Myocardial Oxygen Extraction Research Articles

The Circulatory Effects of Epinephrine Infusion in the Anesthetized Piglet

There are few published data regarding the circulatory effects of systemic epinephrine infusions in newborn subjects. We therefore instrumented six piglets aged 5 to 10 d while they were under pentobarbitone anesthesia for determination of cardiac output, left anterior descending coronary artery flow, systemic and pulmonary pressures, and mixed venous, arterial and coronary sinus gases. Systemic, coronary, and pulmonary vascular resistances, coronary oxygen consumption, and myocardial oxygen extraction ratio were calculated. Epinephrine was infused at doses from 0.2 to 3.2 micrograms/kg/min doubling at 15-min intervals, and measurements were taken after stability had been obtained. Cardiac output increased at the lowest dose investigated, i.e. 0.2 micrograms/kg/min, and progressively increased as the dose was advanced up to 1.6 micrograms/kg/min, decreasing significantly at 3.2 micrograms/kg/min. Blood pressure increased progressively, being significantly above baseline at 0.8, 1.6, and 3.2 micrograms/kg/min and having increased by approximately 81% at the highest dose investigated. Pulmonary arterial pressures were also increased at 1.6 and 3.2 micrograms/kg/min, but only by 35% at the highest dose of 3.2 micrograms/kg/min. Systemic and pulmonary vascular resistances both decreased at the three lower doses investigated and then began to increase progressively; however, the systemic vascular resistance increased to a significantly greater degree than pulmonary vascular resistance. Coronary oxygen consumption increased progressively as the epinephrine dose was increased; however, coronary blood flow and coronary oxygen delivery increased more than oxygen consumption, leading to a progressive reduction in myocardial oxygen extraction ratio and a progressive increase in coronary sinus oxygen content. Whole-body oxygen consumption was increased, but to a lesser extent than systemic oxygen transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Local and neurohumoral control of coronary blood flow.

The powerful local metabolic regulation adjusting coronary blood flow to myocardial oxygen consumption under normal conditions is beyond doubt. However, despite substantial experimental efforts the responsible mediators are still largely unknown. Adenosine, a purported mediator of local metabolic control of coronary blood flow, is probably only involved in transient flow adaptations, but not in steady-state coronary autoregulation. Even below the autoregulatory range a substantial vasodilator reserve persists. Recruitment of such vasodilator reserve results in improved regional myocardial blood flow and attenuated regional ischemic dysfunction. beta-adrenergic coronary dilation is of minor functional importance. alpha-adrenergic coronary constriction acts to attenuate increases in coronary blood flow during sympathetic activation under normal conditions, such that myocardial oxygen extraction increases to match the increased oxygen consumption. alpha-adrenergic coronary constriction remains operative in ischemic myocardium, thus precipitating or contributing to acute myocardial ischemia during sympathetic activation and exercise in experimental animals as well as in patients with stable angina. The vagal transmitter acetylcholine--upon exogenous intracoronary infusion--induces critical constriction of epicardial coronary arteries with endothelial dysfunction and atherosclerosis. However, a vagal initiation of coronary spasm or myocardial ischemia has not been documented so far. Similarly, peptide hormones/transmitters such as NPY, vasopressin, and angiotensin can induce myocardial ischemia upon exogenous administration. Their pathophysiological role in myocardial ischemia and reperfusion, however, remains to be established.

Effect of an oxygen-enriched solution and multiple dosing of antegrade crystalloid cardioplegic solution on myocardial metabolism during coronary artery bypass graft operations

The metabolic effect of excessive oxygenation and frequency of administration of antegrade crystalloid cardioplegic solution was assessed in 33 patients undergoing routine coronary artery bypass graft operations. Four patient groups were designed in which the initial aortic root injection was 1000 ml and then 100 ml administered through the vein grafts after completion of each distal anastomosis. The groups were divided as follows: group 1, single dose, normally oxygenated cardioplegic solution infused via the aortic root; group 2, single dose, high oxygen content cardioplegic solution infused via the aortic root; group 3, normally oxygenated cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes; group 4, high oxygen content cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes. In all groups myocardial mean septal temperature showed an immediate fall to approximately 11 degrees C with the initial aortic root doses and then a gradual rewarming to approximately 20 degrees C during the crossclamp period (mean 58.6 minutes). Metabolic parameters measured or calculated from the coronary sinus effluent were myocardial oxygen extraction, lactate production, base deficit, inorganic phosphate, glucose, potassium, creatine kinase (total and myocardial band fraction), and catecholamine production. There was no statistically significant difference in any of these determinations between each patient group. Furthermore, myocardial recovery, myocardial performance, and postoperative recovery characteristics were not different. We conclude that single or multidose aortic root crystalloid cardioplegic solution (either oxygen enriched or normally oxygenated) is equally effective in routine coronary artery bypass graft operations when septal temperatures are maintained between 15 degrees and 21 degrees C for a total arrest time of 60 minutes or less. In this study, increasing the volume cardioplegic solution given in multiple doses appeared to offer no significant metabolic or functional advantage in patients without complications who had satisfactory left ventricular function.

Myocardial metabolism and adaptation during extreme hemodilution in humans after coronary revascularization.

This study was designed to evaluate the oxygen transport adjustments and myocardial metabolic adaptation that occurs with different levels of hemodilution during normothermia after cardiopulmonary bypass. Prospective, nonrandomized study. Operating room in a university hospital. Eight patients with ejection fractions (> 40%) undergoing elective coronary artery bypass grafting. Before the institution of cardiopulmonary bypass, blood was withdrawn from patients to a target hematocrit of 15%. After coronary artery bypass grafting, a catheter was inserted directly into the coronary sinus. After the patients were rewarmed to 37 degrees C, they were weaned from cardiopulmonary bypass. Hemodynamic indices were measured, as well as measurements of myocardial oxygen consumption (VO2) and myocardial metabolism (lactate extraction and coronary sinus hypoxanthine). Measurements were made at three different hematocrit values: 15%, 20%, and 25%. Hematocrit was increased by autologous blood transfusion. The three levels of hemodilution (hematocrit: 17.4 +/- 3.4%; 23.0 +/- 3.7%; 27.8 +/- 4.8%) were significantly different from baseline (hematocrit 37 +/- 2.6%; p < .05). Oxygen delivery, which increased with autologous transfusion, exceeded 350 mL/min/m2 at each level of dilution. The myocardial VO2 increased significantly after autologous transfusion compared with the most dilute condition (7.0 +/- 3.7 mL/min at hematocrit 17.4% vs. 11.2 +/- 4.8 mL/min at hematocrit 23.0% and 12.4 +/- 4.0 mL/min at hematocrit 27.8%). This transfusion-induced increase was also true of myocardial oxygen extraction. Lactate extraction and hypoxanthine release were normal and unchanged at each level of hemodilution. Systemic oxygen extraction ratio increased with hemodilution and decreased with autologous transfusion. Hemodilution to a hematocrit of approximately 15% is tolerated in anesthetized humans after coronary artery bypass surgery. There was no evidence of myocardial ischemia, as demonstrated by absence of S-T depression on the electrocardiogram, lactate extraction, or hypoxanthine release. In selected patients, postoperative transfusion may be based on systemic physiologic end-points, such as oxygen extraction ratio, rather than set hematocrit values.

Phenylephrine does not limit myocardial blood flow or oxygen delivery during isoflurane-induced hypotension in dogs.

Experiments were performed on seven fentanyl-pentobarbital-anesthetized, open-chest dogs to determine whether stimulation of coronary alpha 1-adrenergic receptors by phenylephrine causes coronary vasoconstriction and impaired myocardial oxygen delivery when phenylephrine is infused to correct isoflurane-induced hypotension. Myocardial blood flow was measured with radioactive microspheres, and myocardial oxygen and lactate extraction were determined. The Fick equation was used to calculate myocardial oxygen consumption. Measurements were obtained (a) under control conditions, (b) after a 30-min inhalation of isoflurane sufficient to decrease mean aortic pressure by 30%, and (c) while maintaining administration of isoflurane, 5-10 min after restoration of mean aortic pressure by intravenous infusion of phenylephrine. Isoflurane-induced hypotension was accompanied by a baroreceptor-mediated increase in heart rate and by a decrease in myocardial oxygen consumption; however, myocardial blood flow was maintained, resulting in decreased oxygen extraction and increased coronary sinus PO2, thus implying a direct coronary vasodilating effect for isoflurane. Lactate extraction was unaffected. Phenylephrine infusion during inhalation of isoflurane returned mean aortic pressure and heart rate to their respective control values, and it did not change myocardial oxygen consumption, myocardial blood flow, myocardial oxygen extraction, coronary sinus PO2, or lactate extraction from values obtained during isoflurane alone. These latter findings are consistent with undiminished coronary vasodilation by isoflurane in the presence of phenylephrine. In conclusion, infused phenylephrine to restore aortic pressure during isoflurane administration had no vasoconstrictor effect in the coronary circulation and did not impair myocardial oxygen delivery. Apparently, the direct coronary vasodilating action of isoflurane completely nullified phenylephrine-induced vasoconstriction via local alpha 1-adrenergic receptors.

Myocardial circulatory and metabolic effects of halothane when used to control intraoperative hypertension in patients with coronary artery disease.

The effect of halothane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anaesthesia, to treat intraoperative hypertension was investigated. Fifteen patients with two- or three-vessel coronary artery disease with an ejection-fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary haemodynamics, global (coronary sinus, CSF) and regional (great cardiac vein, GCVF) myocardial blood flow were measured. Measurements were made: 1) after induction of anaesthesia but prior to skin incision, 2) during sternotomy, and 3) during halothane administration after its use to reduce arterial pressure to the pre-sternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance index (SVRI), and was accompanied by an increase in pulmonary capillary wedge pressure (PCWP), regional myocardial oxygen consumption and extraction, GCFV and CSF. Halothane reduced arterial blood pressure to pre-sternotomy levels within 7.1 +/- 0.6 min at an end-tidal concentration of 0.96 +/- 0.11%. Halothane caused a decrease in SVRI, total coronary vascular resistance, regional myocardial oxygen consumption and extraction, while cardiac index, heart rate and GCVF/CSF ratio remained unchanged. Mean regional myocardial lactate extraction was not affected by sternotomy or halothane. During halothane administration one patient developed regional myocardial lactate production which was not present during sternotomy. However, another two patients, who had regional myocardial lactate production during sternotomy, did not produce lactate or had less negative value of regional myocardial lactate extraction during halothane administration.

Effects of a coronary alpha 1-constriction on transmural left ventricular flow and contractile function.

Modulation of myocardial contractile function and perfusion by alpha 1-adrenergic receptors were examined in anesthetized dogs during left stellate ganglion stimulation. In 11 dogs, stellate stimulation significantly increased heart rate, mean arterial pressure, left ventricular systolic pressure, maximal rate of left ventricular pressure generation, segmental shortening and rate of shortening in anterior and posterior ventricular regions, and myocardial oxygen extraction. Myocardial lactate extraction decreased. The selective alpha 1-adrenergic antagonist prazosin (0.5 mg) injected into the circumflex artery during stellate stimulation caused significant additional increases in maximal rate of left ventricular pressure generation by 19 +/- 5% and in rate of shortening in posterior subendocardium by 20 +/- 6%. No changes were observed in posterior subepicardial or anterior subendocardial segmental contractile function. Myocardial oxygen and lactate extractions returned to their control values following prazosin injection. Regional left ventricular perfusion was measured using tracer microspheres in five additional dogs. Stellate stimulation increased subepicardial and subendocardial perfusion by 30%. Prazosin increased both subepicardial and subendocardial perfusion by an additional 36%. Stellate stimulation increased norepinephrine concentration in the coronary sinus, but no further increase was noted after blockage of alpha 1-receptors by prazosin. Thus, during sympathetic stimulation, an alpha 1-vasoconstriction existed uniformly across the left ventricular wall. However, blockade of this vasoconstriction was associated with an increase in contractile function only in the deeper muscle layers.

Regional cardiac hemodynamics and oxygenation during isovolemic hemodilution in anesthetized pigs.

Hemodilution causes a drop in hematocrit, thereby lowering the oxygen carrying capacity of blood, necessitating an increase in flow or an augmented oxygen extraction by the tissues to meet their oxygen demands. Under normal conditions the myocardial oxygen extraction is already high and the capacity to increase is limited. In the heart the decrease in arterial oxygen content during hemodilution therefore is mainly compensated by an increase in coronary flow. This increase in flow can be achieved by both reduction of the blood viscosity and coronary vasodilatation. The hemodynamic changes during hemodilution may increase myocardial oxygen consumption and, therefore, an even greater increase in coronary flow might be needed.KeywordsMyocardial Blood FlowMyocardial Oxygen ConsumptionOxygen FluxRegional Myocardial Blood FlowArterial Oxygen ContentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Control of coronary vasomotor tone in ischaemic myocardium by local metabolism and neurohumoral mechanisms.

There is no doubt that under normal conditions powerful local metabolic regulation adjusts coronary blood flow to myocardial oxygen consumption. However, despite substantial experimental efforts the responsible mediators are still largely unknown. Adenosine, a purported mediator of local metabolic control of coronary blood flow, is probably only involved in transient flow adaptations but not in steady state coronary autoregulation. Even below the autoregulatory range a substantial vasodilator reserve persists, and recruitment of such a vasodilator results in improved regional myocardial blood flow and attenuated regional ischaemic dysfunction. Beta-adrenergic coronary dilation is of minor functional importance. Alpha-adrenergic coronary constriction acts to attenuate increases in coronary blood flow during sympathetic activation under normal conditions, so that myocardial oxygen extraction increases to match the increased oxygen consumption. Alpha-adrenergic coronary constriction remains operative in ischaemic myocardium, thus precipitating or contributing to acute myocardial ischaemia during sympathetic activation and exercise in experimental animals, as well as in patients with stable angina. The vagal transmitter acetylcholine-upon exogenous intracoronary infusion-induces critical constriction of epicardial coronary arteries with endothelial dysfunction and atherosclerosis. However, a vagal initiation of coronary spasm or myocardial ischaemia has not been documented so far. Similarly, peptide hormones/transmitters such as NPY, vasopressin and angiotensin can induce myocardial ischaemia upon exogenous administration. Their pathophysiological role in myocardial ischaemia, however, remains to be established.

Myocardial Oxygen Supply/Demand Relations During Phenylephrine Infusions in Dogs

Experiments were performed on 14 fentanyl-pentobarbital-anesthetized dogs to assess changes in myocardial oxygen supply/demand relations during intravenous infusions of phenylephrine (2.8 micrograms.kg-1.min-1). Myocardial blood flow was measured with radioactive microspheres. Myocardial oxygen and lactate extraction were determined. Myocardial oxygen consumption was calculated with the Fick equation. In series 1, measurements were obtained during phenylephrine-induced pressor responses. In series 2, measurements were obtained with aortic pressure maintained constant with an extracorporeal reservoir during phenylephrine infusion, so that coronary vasomotor responses could be assessed in the absence of increases in ventricular afterload and perfusion pressure. In series 1, the phenylephrine-induced increase in mean aortic pressure (+42%) was accompanied by proportional (60%) increases in myocardial blood flow and myocardial oxygen consumption and with no change in the endocardium-to-epicardium flow ratio, oxygen extraction, coronary sinus oxygen tension and oxygen saturation, or myocardial lactate extraction. In series 2, phenylephrine infusion caused a transmurally uniform 15% decrease in myocardial blood flow combined with a 10% decrease in myocardial oxygen consumption. The coronary arteriovenous oxygen difference increased modestly (+5%), resulting in small decreases in coronary sinus oxygen tension and oxygen saturation, whereas lactate extraction was unaffected. The present findings suggest that phenylephrine has a direct vasoconstrictor effect in the coronary circulation that is weak and completely overridden by metabolic autoregulatory mechanisms in response to pressure-induced augmentations in cardiac workload. The authors conclude that the myocardium is not at risk when phenylephrine is used to treat hypotension in patients with adequate cardiac function and coronary vasodilator reserve.

Effects of Amiodarone With and Without Polysorbate 80 on Myocardial Oxygen Consumption and Coronary Blood Flow During Treadmill Exercise in the Dog

Since amiodarone has been reported to possess antianginal activity, this study examined the effects of amiodarone on coronary blood flow and myocardial oxygen consumption during exercise. Studies were performed in 14 chronically instrumented dogs trained to run on a motor-driven treadmill. Left circumflex coronary artery blood flow was measured with an electromagnetic flowmeter while aortic and coronary sinus catheters allowed measurement of myocardial oxygen extraction. During control conditions, graded exercise resulted in progressive increases in heart rate, aortic pressure, and coronary blood flow. Two preparations of amiodarone, 5 mg/kg, one dissolved in sterile water and the other in 10% polysorbate 80, were given intravenously to separate groups of dogs. Amiodarone in sterile water caused no hemodynamic changes at rest. However, the increase in heart rate during exercise was blunted after amiodarone, so that heart rate during the heaviest level of exercise was significantly less than during control exercise. Coronary blood flow and myocardial oxygen consumption were unchanged. Amiodarone with polysorbate 80 also blunted the increase in heart rate during exercise, but in addition caused a significant decrease in aortic pressure both at rest and during exercise. Myocardial oxygen consumption and coronary blood flow were significantly decreased after administration of amiodarone with polysorbate 80 at rest and during all exercise levels. Amiodarone with or without polysorbate 80 did not change myocardial oxygen extraction. These data demonstrate that amiodarone exerts a negative chronotropic effect during exercise. However, the decreased arterial pressure and myocardial oxygen consumption were not due to amiodarone, but was seen only with the combination of amiodarone dissolved in polysorbate 80.

Hemodynamic effects and tolerability of intravenous amiodarone in patients with impaired left ventricular function

Acute hemodynamic effects and tolerability of intravenous amiodarone, 5 mg/kg administered over 5 minutes, were compared in patients with coronary artery disease and either a normal (left ventricular [LV] ejection fraction ≥45%, n = 10, group N) or impaired LV function (ejection fraction <45%, n = 9, group L). Amiodarone reduced systemic vascular resistence and LV and aortic pressures in both groups (13%, 18%, and 13%, respectively [group N], and 15%, 17%, and 15%, respectively [group L]) over the short term. Heart rate initially increased (18%, group L, and 10% group N), but was followed by a late 6% decrease in group N only, and by a progressive reduction in contractility (V max), together with a rise in LV end-diastolic pressure (19% and 38%, respectively [group N] and 17% and 58%, respectively [group L]; all values p < 0.05 versus control). Coronary flow increased significantly by 20% (group N) and 31% (group L), but only during amiodarone administration, accompanied by a 26% and 25% reduction in myocardial oxygen extraction in groups N and L, respectively. Stroke work decreased in both groups (20% [group N] and 19% [group L], p < 0.05 versus control). In contrast, cardiac output only improved (10%) in patients with impaired ventricular function. Significant side effects did not occur. Thus relatively high dosages of intravenous amiodarone are well tolerated and improve cardiac pump function in patients with an impaired, but not with a normal cardiac function. However, the tendency to increase LV end-diastolic pressures necessitates careful monitoring in patients in whom preexisting LV filling pressure may be elevated.

Combined dynamic and gated C-11 acetate pet imaging provides estimates of myocardial oxygen extraction and wall tension

Combined dynamic and gated C-11 acetate pet imaging provides estimates of myocardial oxygen extraction and wall tension

Effect of beta-adrenergic blockade on myocardial function and energetics in congestive heart failure. Improvements in hemodynamic, contractile, and diastolic performance with bucindolol.

The hemodynamic effects of beta-adrenergic blockade with bucindolol, a nonselective beta-antagonist with mild vasodilatory properties, were studied in patients with congestive heart failure. Fifteen patients (New York Heart Association class I-IV) underwent cardiac catheterization before and after 3 months of oral therapy with bucindolol. The left ventricular ejection fraction increased from 0.23 +/- 0.12 to 0.29 +/- 0.14 (p = 0.007), and end-systolic elastance, a relatively load-independent determinant of contractility, increased from 0.60 +/- 0.40 to 1.11 +/- 0.45 mm Hg/ml (p = 0.0049). Both left ventricular stroke work index (34 +/- 13 to 47 +/- 19 g-m/m2, p = 0.0059) and minute work (5.5 +/- 2.2 to 7.0 +/- 2.6 kg-m/min, p = 0.0096) increased despite reductions in left ventricular end-diastolic pressure (19 +/- 8 to 15 +/- 5 mm Hg, p = 0.021). There was an upward shift in the peak + dP/dtmax-end-diastolic volume relation (p = 0.0005). These data demonstrate improvements in myocardial contractility after beta-adrenergic blockade with bucindolol. At a matched paced heart rate of 98 +/- 15 min-1, the time constant of left ventricular isovolumic relaxation was significantly reduced by bucindolol therapy (92 +/- 17 versus 73 +/- 11 msec, p = 0.0013), and the relation of the time constant to end-systolic pressure was shifted downward (p = 0.014) with therapy. The slope of the logarithm left ventricular end-diastolic pressure-end-diastolic volume relation was unchanged (p = 0.51) after bucindolol. These data suggest that chronic beta-adrenergic blockade with bucindolol improves diastolic relaxation but does not alter myocardial chamber stiffness. Myocardial oxygen extraction, consumption, and efficiency were unchanged despite improvement in contractile function and mechanical work. Thus, in patients with congestive heart failure, chronic beta-adrenergic blockade with bucindolol significantly improves myocardial contractility and minute work, yet it does not do so at the expense of myocardial oxygen consumption. Additionally, bucindolol improves myocardial relaxation but does not affect chamber stiffness.

Role of Adenosine in Catecholamine-Induced Global Coronary Functional Hyperemia in Isolated Guinea Pig Hearts

This study was designed to test the hypothesis that endogenous adenosine participates in the global coronary functional hyperemia accompanying intracoronary infusions of norepinephrine (NE) and isoproterenol (ISO). Intracoronary adenosine deaminase (ADA) was employed to test the hypothesis in isolated, perfused guinea pig hearts. We measured coronary perfusate flow (CPF) at a constant coronary perfusion pressure. Heart rate (HR), left ventricular pressure, and its rate of development were also measured. Global myocardial oxygen consumption (MVO2) and oxygen extraction were calculated, and blood gases and pH were measured routinely in inflow and outflow perfusate samples. In the absence of ADA, NE and ISO increased HR 67 +/- 6 and 106 +/- 11 beats.min-1, left ventricular pressure development 519 +/- 46 and 375 +/- 35 mm Hg.s-1, MVO2 22 +/- 2 and 28 +/- 3 microliters.min-1.g-1, and CPF 1.6 +/- 0.2 and 2.2 +/- 0.2 ml.min-1.g-1, respectively. With constant infusion of ADA (4.5 U.min-1.g-1, a dose which produces no direct effects on cardiac function) for 4 min, similar increments in HR and left ventricular pressure development were achieved with both catecholamines. Corresponding changes in MVO2 (9 +/- 2 and 6 +/- 3 microliters.min-1.g-1) were significantly less than those seen in the absence of ADA. Moreover, CPF did not increase in response to NE and ISO in the presence of ADA. These findings support an important role for adenosine in catecholamine-induced global coronary functional hyperemia in isolated, perfused guinea pig hearts.

Effect of high dose norepinephrine versus epinephrine on cerebral and myocardial blood flow during CPR

Several animal studies have demonstrated an improvement in cerebral blood flow (CBF) and myocardial blood flow (MBF) after the administration of epinephrine (E) 0.20 mg/kg during closed chest CPR. The administration of norepinephrine (NE) in doses of 0.12 and 0.16 mg/kg demonstrated a trend toward improved CBF and MBF during CPR over that seen with E 0.20 mg/kg in the same animal model. The purpose of this study was to compare the effects of a higher dose of NE 0.20 mg/kg to E 0.20 mg/kg to determine if increasing doses of NE would demonstrate further improvement in CBF and MBF during CPR. Fourteen immature swine were anesthetized and instrumented for regional blood flow and hemodynamic measurements. After 10 min of ventricular fibrillation (VF), CPR was begun using a mechanical thumper. After 3 min of CPR, the animals received either E 0.20 mg/kg (n = 7) or NE 0.20 mg/kg (n = 7) through a right atrial catheter. CPR was continued for an additional 3.5 min and defibrillation was then attempted. CBF (ml/min/100 g), MBF (ml/min/100 g), myocardial oxygen delivery (MDo2; ml O2/min/100 g), myocardial oxygen consumption (MVo2; ml O2/min/100 g), and myocardial oxygen extraction ratios (ER, MVo2/MDo2) were measured during normal sinus rhythm (NSR), during CPR, and during CPR following drug administration. Following drug administration, CBF, MBF, MDo2 and MVo2 rose while ER fell in both E and NE groups. There were no significant differences between groups in CBF, ER, or intravascular pressures following drug administration (P greater than or equal to 0.07). The NE group demonstrated significantly higher MBF (118.9 +/- 73.1 vs. 62.2 +/- 45.3, P = 0.04), MVo2 (14.2 +/- 7.7 vs. 7.0 +/- 3.8, P = 0.05), and MDo2 (19.9 +/- 13.4 versus 9.4 +/- 6.3, P = 0.05) compared to the E group following drug administration While NE improved MBF and MDo2 over E during CPR, there was a trend toward lower resuscitation rates with NE (57.1% vs. 85.7% P = 0.56). Any benefit of higher MBF and MDo2 with NE 0.20 mg/kg appears to be offset by proportionately high MVo2 and a trend toward lower resuscitation rates in the NE 0.20 mg/kg animals.

Coronary circulation in acute hypoxia

Healthy young men were subjected to different degrees of hypoxia at rest and during increased levels of cardiac work induced by atrial pacing and physical exercise at submaximal and maximal loads. Coronary sinus (cs) blood flow was measured by thermodilution and a-cs differences of O2 and lactate were obtained. At low cardiac power output (rest, pacing) the reduction in arterial oxygen content was compensated for mainly by a more complete myocardial oxygen extraction producing lowered cs O2 saturation and tension, while at higher cardiac power (exercise) the compensatory mechanism was entirely an increased coronary blood flow. It was possible to compensate fully for a reduction in arterial O2 saturation of 9% even during maximal physical exercise. With a reduction in arterial oxygen content of more than 20-25% the flow increase was sufficient to supply the heart with enough O2 during submaximal (heart rate 157 beats min-1) but not maximal exercise, in which case anaerobic glycolysis contributed significantly to the myocardial energy metabolism. It is concluded that the normal heart has a 'coronary flow reserve' of about 33% above the flow prevailing during maximal physical exercise under air breathing.

Role of thromboxane A2 in the cardiovascular response to intracoronary C5a.

Intracoronary administration of complement component C5a induces transient decreases in coronary blood flow and regional left ventricular segment shortening, associated with intramyocardial granulocyte trapping. We evaluated the influence of a cyclooxygenase inhibitor (acetylsalicylic acid, n = 8) or a thromboxane A2/prostaglandin H2 receptor antagonist (SQ29548, n = 6) on these C5a-induced cardiovascular responses. Open-chest anesthetized pigs were instrumented to monitor heart rate, arterial blood pressure, left anterior descending coronary blood flow, regional left ventricular segment shortening, and dP/dt. Oxygen content, lactate concentration, leukocyte count, and thromboxane B2, the stable metabolite of thromboxane A2, were measured in arterial and regional coronary venous blood. Repetitive injections of intracoronary C5a (500 ng) given 60 minutes apart showed no tachyphylaxis of the hemodynamic response. However, tachyphylaxis was seen in coronary blood flow changes when injections were spaced 30 minutes apart. An increase in myocardial oxygen extraction and lactate production was observed after intracoronary C5a. Administration of acetylsalicylic acid (50 mg/kg i.v.) attenuated C5a-induced decreases in coronary blood flow (-8 +/- vs. -3 +/- 1 ml/min) and regional left ventricular segmental shortening (-10 +/- 3% vs. -2 +/- 1%) and blocked the maximal increase in coronary venous thromboxane B2 (2.0 +/- 0.1 vs. 0.2 +/- 0.1 pmol/ml plasma). Furthermore, SQ29548 (30 micrograms/kg/min) reduced C5a-induced changes in coronary blood flow (-13 +/- 2 vs. -4 +/- 2 ml/min) and segmental shortening (-14 +/- 2% vs. -3 +/- 1%). Neither cyclooxygenase inhibition nor thromboxane A2/prostaglandin H2 antagonism blocked the decrease in coronary venous granulocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine versus methoxamine in survival postventricular fibrillation and cardiopulmonary resuscitation in dogs

Previous studies have indicated that methoxamine (an alpha adrenergic receptor agonist) may provide an advantage compared to epinephrine (a mixed alpha and beta adrenergic agonist) during cardiac arrest and CPR. To test this theory, we compared the effects of bolus injections of epinephrine vs. methoxamine on survival, hemodynamic variables, blood gases, and blood lactate concentrations during ventricular fibrillation and CPR in 12 dogs. Each dog underwent a 3-min fibrillatory arrest followed by 10 min of fibrillation and CPR, at which time the animals were defibrillated. Epinephrine (0.05 mg/kg, n = 6) or methoxamine (2 mg/kg, n = 6) was administered at the start of CPR. Both epinephrine and methoxamine produced identical survival rates (5/6) with no differences in coronary perfusion pressure gradients or blood gases (aortic, venous, or great cardiac venous pH, PaO2, or PaCO2) during CPR. Also, there were no differences between the two study groups in myocardial lactate or oxygen extraction ratios during CPR. We conclude that in the dosages tested in our experimental model, epinephrine and methoxamine produce similar results in the variables which we measured.

Myocardial circulatory and metabolic effects of halothane when used to control intraoperative hypertension in patients with coronary artery disease

The effect of halothane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anaesthesia, to treat intraoperative hypertension was investigated. Fifteen patients with two- or three-vessel coronary artery disease with an ejection-fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary haemodynamics, global (coronary sinus, CSF) and regional (great cardiac vein, GCVF) myocardial blood flow were measured. Measurements were made: 1) after induction of anaesthesia but prior to skin incision, 2) during sternotomy, and 3) during halothane administration after its use to reduce arterial pressure to the pre-sternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance index (SVRI), and was accompanied by an increase in pulmonary capillary wedge pressure (PCWP), regional myocardial oxygen consumption and extraction, GCFV and CSF. Halothane reduced arterial blood pressure to pre-sternotomy levels within 7.1 +/- 0.6 min at an end-tidal concentration of 0.96 +/- 0.11%. Halothane caused a decrease in SVRI, total coronary vascular resistance, regional myocardial oxygen consumption and extraction, while cardiac index, heart rate and GCVF/CSF ratio remained unchanged. Mean regional myocardial lactate extraction was not affected by sternotomy or halothane. During halothane administration one patient developed regional myocardial lactate production which was not present during sternotomy. However, another two patients, who had regional myocardial lactate production during sternotomy, did not produce lactate or had less negative value of regional myocardial lactate extraction during halothane administration.