Coronary Sinus Oxygen Content Research Articles

Effects of digoxin on myocardial oxygen supply and demand in patients following coronary artery bypass surgery.

Although digoxin is used frequently in patients in the prophylaxis of postoperative supraventricular tachyarrhythmias, the effects of the drug on myocardial oxygen supply and demand after coronary bypass have not been described. Seven adult patients with good ventricular function who underwent myocardial revascularization were studied before and three hours after digoxin (0.5 mg, iv). There were no significant changes observed in any measured systemic hemodynamic variable. Evaluation of global myocardial metabolism showed an increase in myocardial oxygen consumption (P less than 0.05) which was compensated satisfactorily, as no significant alteration was noted in the coronary sinus oxygen content, or in the lactate gradient across the myocardium. Since the authors studied the effects of only one dose of digoxin, the effects of full digitalization in these patients remains to be defined.

Effects of Protamine Sulfate on Myocardial Oxygen Supply and Demand in Patients following Cardiopulmonary Bypass

The effect of protamine sulfate on myocardial oxygen supply and demand was studied under clinical conditions in nine patients following cardiopulmonary bypass. Before surgery, the patients had severe coronary artery disease with good ventricular function. The patients required no vasoactive drugs, but only blood volume adjustments when weaned off bypass, and were hemodynamically stable at the time of study. The protamine dose of 196 mg (2.5 mg/kg) was infused over 4 +/- 1 minutes. Although modest variation in hemodynamic function occurred in individual patients after administration of protamine, there were no significant hemodynamic alterations for the group. No significant alteration in global myocardial metabolism was observed. Protamine caused a small decrease in measured coronary blood flow, resulting in a corresponding reduction in calculated myocardial oxygen consumption as coronary sinus oxygen content remained unaltered. Myocardial lactate extraction showed no significant alteration. It is concluded that protamine sulfate, given at rapid infusion rates in hemodynamically stable patients, is not associated with an adverse alteration in hemodynamics or global myocardial metabolism.

Cardiovascular Effects of Morphine in Patients with Coronary Arterial Disease

Large doses of morphine sulfate have been reported to cause myocardial lactate production and reduction in coronary blood flow in animals. Similar effects with clinical doses in man would significantly alter the management of cardiac patients. Eleven adult patients with significant coronary arterial disease and normal left ventricular ejection fraction were studied before and 30 minutes after infusion of morphine (0.25 mg/kg IV). Evaluation of myocardial metabolism showed an increase in coronary sinus oxygen content (p < 0.001) and a reduction in myocardial oxygen consumption. Myocardial lactate extraction was not altered. No change in coronary sinus blood flow was seen. It is concluded that infusion of morphine sulfate, 0.25 mg/kg IV, does not produce global myocardial ischemia in patients with coronary artery disease and normal ventricular function.

Correlates of Myocardial Oxygen Consumption when Afterload Changes during Halothane Anesthesia in Dogs

We have examined whether several clinically measurable correlates of myocardial oxygen consumption remain valid correlates when afterload changes during morphine or halothane plus morphine anesthesia. The correlates measured were heart rate, systolic blood pressure, left ventricular end diastolic pressure (LVEDP), and rate-pressure product (RPP). In six dogs we measured myocardial oxygen consumption (mVO2) and hemodynamic variables during morphine (4 mg/kg) and during morphine-halothane (1.5% end tidal concentration) anesthesia. We changed ventricular afterload by infusion of nitroprusside or phenylephrine and measured mVO2 as the product of left anterior descending coronary artery flow and arterial-coronary sinus oxygen content difference. RPP was the best correlate of mVO2 during both morphine-halothane (R = 0.84) and morphine anesthesia (R = 0.71). Systolic pressure and LVEDP also significantly correlated with mVO2 during both anesthetic states. The slope of the line relating RPP and mVO2 was significantly (p < 0.05) depressed during added halothane anesthesia. This slope depression (0.016 vs 0.021) is of little practical consequence within the physiologic range of RPP. Regression analysis showed that systolic pressure and heart rate alone account for the major part of changes in mVO2 during morphine-halothane anesthesia under the conditions of this experiment. After allowing for changes in LVEDP associated with systemic pressure, LVEDP still had significant effects on mVO2 during morphine anesthesia, but not during morphine-halothane anesthesia. We conclude that RPP is the best correlate of mVO2 under morphine-halothane anesthesia over a wide range of ventricular afterload states.

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.

Alteration in myocardial oxygen balance during exercise after beta-adrenergic blockade in dogs.

The effects of beta-adrenergic blockade upon myocardial blood flow and oxygen balance during exercise were evaluated in eight conscious dogs, instrumented for chronic measurements of coronary blood flow, left ventricular pressure, aortic blood pressure, heart rate, and sampling of arterial and coronary sinus venous blood. The administration of propranolol (1.5 mg/kg iv) produced a decrease in heart rate, peak left ventricular (LV) dP/dt, LV (dP/dt/P, and an increase in LV end-diastolic pressure during exercise. Mean coronary blood flow and myocardial oxygen consumption were lower after propranolol than at the same exercise intensity in control conditions. The oxygen delivery-to-oxygen consumption ratio and the coronary sinus oxygen content were also significantly lower. It is concluded that the relationship between myocardial oxygen supply and demand is modified during exercise after propranolol, so that a given level of myocardial oxygen consumption is achieved with a proportionally lower myocardial blood flow and a higher oxygen extraction.

The effect of carbon dioxide upon myocardial contractile performance, blood flow and oxygen consumption.

1. Mongrel dogs were anaesthetized with chloralose, paralysed, ventilated and vagotomized and given a beta-blocking drug, sotalol, in sufficient doses to block the effects of 5 microgram of adrenaline. 2. Changes in inspired CO2 concentration were produced, causing increases of arterial PCO2 up to 120 mmHg. The effects on myocardial blood flow were measured with radioactive microspheres. Coronary sinus and arterial blood was sampled. 3. In the absence of beta-blockade, an increase in arterial PCO2 produced variable effects. In some dogs coronary blood flow increased, while in others there was no change. There was a mean increase in coronary blood flow at arterial PCO2 values above 85 mmHg which was abolished by beta-blockade. 4. In the presence of beta-blockade, an increase of arterial PCO2 produced depression of left ventricular performance, i.e. a fall of maximum rate of rise of left ventricular pressure and a rise of left ventricular end-diastolic pressure. 5. In the presence of beta-blockade, there were no consistent changes in myocardial blood flow, left ventricular pressure or cardiac output. 6. In the absence of beta-blockade, coronary arterial minus venous ocygen content was reduced by hypercapnia. In the presence of beta-blockade, the changes were small and not statistically significant. The direct coronary vasodilator effect was therfore negligible. 7. It is concluded that the previously reported hypercapnic vasodilatation was mainly an effect of sympatho-adrenergic stimulation by hypercapnia. 8. In the presence of beta-blockade, coronary sinus PO2 increased markedly, with little change in coronary sinus oxygen content; this was consistent with a shift to the right of the oxy-haemoglobin dissociation curve. Under circumstances of hypercapnia, a rise in coronary sinus (and presumably tissue) PO2 failed to produce vasoconstriction. 9. It is argued that the vasodilator effect of hydrogen ions and the vasoconstrictor effect of oxygen probably cancel one another when the arterial PCO2 is raised.

Elevated mid-myocardial oxygen tension in the fibrillating heart during cardiopulmonary bypass.

Mid-myocardial tissue oxygen tension was measured in the left ventricular wall of the hearts of ten dogs by means of a Silastic tonometer implanted earlier. During cardiopulmonary bypass, myocardial PO2 was significantly higher in a spontaneously fibrillating heart (5.4 +/- 0.9 kPa) than during the initial beating period (3.7 +/- 0.5 kPa) or after defibrillation (4.0 +/- 0.7 kPa). In general, there was a tendency towards increased myocardial blood flow, elevated oxygen uptake and reduced coronary sinus oxygen content during ventricular fibrillation, compared with the situation in the beating heart. Myocardial lactate extraction remained unchanged during the different phases of cardiopulmonary bypass. The increase in mid-myocardial oxygen tension during ventricular fibrillation was probably due to increased total myocardial blood flow and redistribution of regional myocardial circulation. In two additional dogs, ventricular fibrillation resulted in left ventricular distension and a simultaneous fall of myocardial oxygen tension, which indicates the necessity of left ventricular decompression suction in a fibrillating heart during cardiopulmonary bypass.

Prostacyclin (PGI2) induces coronary vasodilatation in anaesthetised dogs

Prostacyclin (PGI2), the predominant metabolite of arachidonic acid in isolated hearts, relaxes strips of bovine coronary artery and is a potent vasodilator in isolated perfused hearts. We have examined the actions of prostacyclin on coronary blood flow in open chest dogs anaesthetised with chloralose. An electromagnetic flow probe was fitted to the left circumflex artery and phasic coronary flow, mean coronary flow (a measure of coronary volume flow over 4 s intervals), and coronary vascular resistance were recorded together with aortic pressure and heart rate. Intravenous infusion of prostacyclin (0.05 to 1.0 microgram.kg.1.min.1), reduced coronary vascular resistance and aortic pressure according to dose, but had only small effects on phasic coronary flow or mean coronary flow. Both tachycardia and bradycardia occurred during infusion of prostacyclin, but 6-oxo-prostaglandin F1alpha (infused at 10 micrograms.kg-1.min-1), the stable degradation produce of prostacyclin, had no cardiovascular effects. The coronary vasodilator effects of prostacyclin were clear when it was injected into the left circumflex artery via a fine catheter distal to the flow probe. Prostacyclin (0.05 to 0.5 microgram) increased phasic coronary flow and mean coronary flow up to 3 fold and reduced coronary vascular resistance without affecting aortic pressure or heart rate, although higher doses had systemic effects. Prostaglandin E1 (0.1 to 0.5 microgram), which also dilated the coronary vessels, had a longer lasting effect and was 1 to 4 times more potent than prostacyclin. Prostaglandin E2, (0.5 to 4 microgram) was less potent than prostacyclin. In four dogs prostacyclin (20 to 500 micrograms) applied epicardially to the left ventricle caused marked and prolonged coronary vasodilatation. Epicardial application of prostacyclin (10 to 25 micrograms) to the right ventricle increased coronary sinus oxygen content with minimal changes in blood pressure. The endoperoxide prostaglandin H2 was a coronary vasodilator of similar potency to prostacyclin, but its analogue U46619 is a vasoconstrictor. Inhibition of cyclo-oxygenase with indomethacin (5 mg.kg-1 i.v.) or sodium meclofenamate (2 mg.kg-1 i.v.) potentiated the coronary dilator effects of prostacyclin given intravenously or into the coronary artery. Cyclo-oxygenase inhibition did not alter the hypotensive effects and increased the coronary vasodilator potency of prostacyclin relative to prostaglandin E2. Thus the sensitivity of the coronary vascular bed to prostacyclin is enhanced when endogenous biosynthesis of prostaglandin-like substances is inhibited. Although the importance of arachidonic acid metabolites in the coronary circulation still requires validation in vivo, it is clear that prostacyclin, and not prostaglandin E2, is the prostaglandin most likely to be involved.

CHANGES IN CANINE MYOCARDIAL BLOOD FLOW AND OXYGEN CONSUMPTION IN RESPONSE TO HALOTHANE

The effect of 0.5, 1 and 1.5 per cent inspired halothane concentrations on myocardial blood flow has been studied using a xenon-133 clearance technique in 12 dogs anaesthetized with pentobarbitone 30 mg/kg body weight. Halothane was found to reduce cardiac output, mean systemic arterial pressure, myocardial blood flow and oxygen consumption in proportion to its inspired concentration. With the higher concentrations of halothane, there was a small increase in myocardial vascular resistance associated with a small, significant reduction in coronary sinus Po2 and oxygen content.

Influence of frequency of atrial contraction on coronary blood flow and ventricular performance in the conscious dog with myocardial infarction.

The effects of alterations in the frequency of contraction on coronary blood flow and ventricular performance were studied in 12 conscious, unsedated dogs with established myocardial infarction. Total and regional coronary blood flow was measured using radioactive microspheres. The peak increase in flow to the right ventricle was 71% to the infarcted area of the left ventricle was 72% to the non-infarcted area of the left ventricle was 90% and to the ventricular septum was 104%. Despite the generalized increases in regional myocardial blood flow, flow tended to decrease to the subendocardial portion of the infarcted area of the left ventricle. The peak increases in coronary flow and the reduction in flow to the subendocardial portion of the infarcted area occurred at a heart rate of approximately 200/min provided by atrial pacing. Myocardial contractility, as evidenced by peak increases of 16% in maximum LV dP/dt and 12% in dP/dtP, was only enhanced with abrupt incremental changes in heart rate and not with continuous atrial pacing over 15-min periods. Despite the generalized increases in coronary perfusion coronary sinus oxygen content decreased with a widening of the coronary arteriovenous oxygen difference indicating increased myocardial oxygen usage. Thus increasing frequency of contraction in myocardial infarction results in a slight initial but not sustained inotropic effect, a moderate and generalized increase in regional myocardial blood flow, increased myocardial oxygen consumption, and the potential for subendocardial extension of the area of myocardial damage within the infarcted area.

Pentaerythritol trinitrate and glyceryl trinitrate on myocardial oxygen consumption and haemodynamics in the dog.

1. The effects of pentaerythritol trinitrate (pentrinitrol) and glyceryl trinitrate on myocardial oxygen consumption and myocardial and systemic haemodynamics were studied in anaesthetized open-chest dogs. An in vivo oximeter in the coronary sinus permitted continuous determination of arteriovenous oxygen difference and myocardial oxygen consumption. All parameters were determined simultaneously at various intervals after drug administration. 2. Myocardial oxygen consumption was diminished by both nitrates for more than 16 min. Changes in arteriovenous oxygen difference and coronary sinus oxygen content were variable between drugs. Following an initial transient increase, coronary blood flow was reduced by both nitrates. Aortic blood pressure, aortic blood flow, left ventricular end-diastolic pressure and left ventricular dP/dt were also reduced. Heart rate and contractile force were not appreciably altered by either nitrate. 3. The decrease in myocardial oxygen consumption appears to be associated with the haemodynamic profile of these drugs. Both nitrates produced comparable reductions in preload (left ventricular end-diastolic pressure) and afterload (aortic pressure) as well as dP/dt.

SYSTEMIC AND CORONARY HAEMODYNAMIC EFFECTS OF KETAMINE IN INTACT ANAESTHETIZED AND UN ANAESTHETIZED DOGS

Ten intact anaesthetized dogs breathing room air spontaneously (Group A) were compared with ten artificially ventilated dogs (Group B). All were given a bolus of ketamine 2 mg/kg followed by a 20-min infusion of ketamine 0.1 mg/kg/min. In Group A, coronary sinus blood flow, measured with a thermodilution flowmeter, increased by 90% while coronary vascular resistance decreased by 28% and coronary sinus oxygen content decreased by 27%. Heart rate increased by 47%, and arterial pressure by 9%. Cardiac output, calculated by the dye dilution method, increased by 29%, while the left ventricular work index decreased by 50%. Minute ventilation rate decreased by 55%. The Group B dogs were studied as described above, except that they were artificially ventilated. The haemodynamic ahanges were less in Group B, possibly because of improved arterial oxygenation. Heart rate increased by 24%, cardiac output by 21% and arterial pressure by 2%. The coronary sinus blood flow increased by 12% while coronary vascular resistance decreased by 11%. Coronary sinus oxygen concentration decreased by 15%. Five unanaesthetized dogs with electromagnetic flowmeter probes chronically implanted on the aorta and circumflex coronary artery, and an indwelling arterial catheter were studied before, during and after the intravenous administration of ketamine 2, 4, and 8 mg/kg. A dose of 8 mg/kg produced increases in cardiac output, heart rate and arterial pressure of 21%, 44% and 24%, respectively, while coronary blood flow increased 47%. We conclude that, in healthy dogs, ketamine produces an increase in heart rate and cardiac work. A significant increase in coronary blood flow appears to be insufficient to meet the metabolic demands of the myocardium, as the coronary sinus oxygen content decreased.

CHANGES IN CANINE MYOCARDIAL BLOOD FLOW AND OXYGEN CONSUMPTION IN RESPONSE TO HALOTHANE

The effect of 0.5, 1 and 1.5 per cent inspired halothane concentrations on myocardial blood flow has been studied using a xenon-133 clearance technique in 12 dogs anaesthetized with pentobarbitone 30 mg/kg body weight. Halothane was found to reduce cardiac output, mean systemic arterial pressure, myocardial blood flow and oxygen consumption in proportion to its inspired concentration. With the higher concentrations of halothane, there was a small increase in myocardial vascular resistance associated with a small, significant reduction in coronary sinus Po2 and oxygen content.

Systemic and coronary hemodynamic effects of glucagon

The systemic and coronary hemodynamic effects of glucagon have been studied in anesthetized mongrel dogs. Administration of this agent produced an increase in cardiac rate, a decrease in systemic arterial pressure and increases in body and cardiac oxygen consumption. Arterial hemoglobin, hematocrit and oxygen content increased as did mixed venous oxygen content, but the coronary sinus oxygen content decreased. Cardiac output and coronary blood flow increased, but peripheral and coronary vascular resistances decreased. The systemic and coronary hemodynamic effects of glucagon were similar during beta adrenergic blockade induced by propranolol.

Effect of propranolol on systemic and coronary hemodynamics at rest and during simulated exercise.

The systemic and coronary hemodynamic effects of relatively large doses of propranolol have been studied following its infusion into intact anesthetized dogs at rest and during simulated exercise. At rest, the administration of propranolol was associated with decreased cardiac output and ventricular work and increased peripheral, pulmonary, and coronary vascular resistances. Coronary blood flow and coronary sinus oxygen content decreased while myocardial oxygen consumption and the index of cardiac efficiency were unchanged. The usual hemodynamic response to mild exercise was obtained, with increased cardiac output, cardiac work, body oxygen consumption, and a modest but insignificant increase in coronary blood flow. When propranolol was given and the same exercise continued, body oxygen consumption, cardiac output, and left ventricular work significantly decreased. Insignificant decreases occurred in coronary blood flow, left ventricular oxygen usage, and coronary sinus oxygen content. The present observations are consistent with the thesis that beta-adrenergic blockade induced by propranolol decreases cardiac work at rest and reduces the cardiovascular response to exercise.

SYSTEMIC AND CORONARY HEMODYNAMIC EFFECTS OF PSEUDOEPHEDRINE.

Conclusions1. Pseudoephedrine hydrochloride has been administered to a group of anesthetized mongrel dogs in a dose of 1 or 2 mg/kg/minute. Systemic and coronary hemodynamics have been determined before and during its administration. 2. A minor but consistent increase occurred in systemic arterial pressure accompanied by a decrease in cardiac rate. 3. There was a slight but significant increase in hematocrit and in coronary sinus oxygen content. 4. No significant change occurred in cardiac output, coronary blood flow or other measured parameters, consequently the hemodynamic effects may be considered to be minimal.

The systemic and coronary hemodynamic effects of diazoxide

1. 1. Hemodynamic studies, including the determination of cardiac output and coronary blood flow, have been made before and after the intravenous administration of diazoxide to anesthetized intact dogs and unanesthetized man. The response was essentially the same in the dog and in man. 2. 2. Administration of this agent intravenously was accompanied by an acute reduction in peripheral, total pulmonary, and coronary resistances, with a decrease in systemic and pulmonary arterial pressures and an increase in cardiac output and coronary blood flow. 3. 3. Coronary sinus oxygen content increased, with the per cent increase in coronary blood flow significantly greater than the change in cardiac rate, left ventricular work, and left ventricular oxygen consumption. 4. 4. The acute hemodynamic effects of diazoxide in control animals are not significantly different from the effects in animals pretreated with chlorothiazide or small doses of reserpine. 5. 5. Although both diazoxide and chlorothiazide are benzothiadiazine derivatives, their acute hemodynamic effects differ greatly.

Systemic and Coronary Hemodynamic Effects of Hexadylamine.

Summary1. Systemic and coronary hemodynamics have been determined in a series of 10 intact anesthetized mongrel dogs by the Fick principle and nitrous oxide method respectively, before and during a constant intravenous infusion of hexadylamine (MRL 38, dicyclohexyl-piperidyl-ethylene hydrochloride). 2. Administration of hexadylamine produced peripheral and coronary vasodilatation, as well as increased cardiac output and coronary blood flow. 3. The coronary sinus oxygen content increased significantly, with narrowing of the myocardial arteriovenous oxygen difference. 4. Left ventricular work and myocardial oxygen consumption increased slightly but insignificantly.

Effect of serotonin (5-hydroxytryptamine) on the systemic and coronary vascular bed of the dog

Dogs were anesthetized with morphine and Dial-urethane-Nembutal. Cardiac output (Fick) and coronary blood flow (N2O Fick) were measured before and after the mechanical infusion of 20 µg/kg/ min. of serotonin over a period of 25 minutes. The results showed an increase in heart rate, pulmonary arterial pressure and right ventricular work. Systemic blood pressure and resistance were reduced. Coronary blood flow increased by 79%, with an increase of coronary sinus oxygen content of 3.3 vol. %. Cardiac O2 consumption and CO2 production increased. Mechanical efficiency of the left ventricle fell by 3%. Serotonin appears to act as a powerful coronary vasodilator, increasing the oxygen supply to the myocardium without increasing left ventricular work.