Autoregulation Of Coronary Blood Flow Research Articles

Arterial hypertension. Does the J curve exist? And then?

The concept that 'the lower the blood pressure (BP) achieved the better the outcome' rests on the demonstration of a direct relationship between BP and incident outcomes, down to levels of 115 mmHg of systolic BP (sBP) and 75 mmHg of diastolic BP (dBP) carried out in 1 million individuals from 61 cohorts recruited between 1950 and 1990 and followed for about 14 years. The alternative to the 'lower the better' concept is the hypothesis of a J-shaped relationship, according to which the benefits of reducing sBP or dBP to low values may be dangerous leading even to an increase in total mortality and/or in CV outcomes. Data from contemporary epidemiologic observations, (CALIBER study), showed that the relationships between rising BP and increased incidence of outcomes rise continuous even over 85 years of age without the evidence of a J-shaped association with any of the outcomes at any age strata. In the English Longitudinal Study of Ageing study (ELSA), a tailored analysis for octogenarians showed that the increase in mortality rates associated with BP ranges appears at sBP <110 mmHg and ≥170 mmHg. In randomized controlled trials (SPRINT, HYVET and INVEST), the J curve seems to concern mainly patients with an extensive atherosclerotic burden, rather than. An impaired autoregulation of coronary blood flow (CBF) leading to a fall in diastolic BP and resulting in a lowering in the perfusion pressure distal to the epicardial coronary artery stenosis, can eventually lead to myocardial ischemia. Diastolic dysfunction can concur in worsening CBF in diastole. These features are often seen in elderly patients with heart failure with preserved ejection fraction. The steeper position of the slope of the end-systolic elastance can lead to dramatic increases and decreases in BP for the same change in afterload or preload. This may explain why elderly hypertensives are more prone to suffer of hypertensive crisis and/or hypotension than younger hypertensives. "Pseudo-hypertension" caused by structural sclerotic changes in the brachial artery wall may cause overtreatment related falls in blood pressure. Thus, the J curve exists but only in patients with multiple comorbidities and/or extensive atherosclerotic burden.

Role of PET to evaluate coronary microvascular dysfunction in non-ischemic cardiomyopathies.

Coronary microvascular dysfunction (CMD) can result from structural and functional abnormalities at the intramural and small coronary vessel level affecting coronary blood flow autoregulation and consequently leading to impaired coronary flow reserve. CMD often co-exists with epicardial coronary artery disease but is also commonly seen in patients with various forms of heart disease, including dilated, hypertrophic, and infiltrative cardiomyopathies. CMD can go unnoticed without any symptoms, or manifest as angina, and/or dyspnea, and contribute to the development of heart failure, and even sudden death especially when co-existing with myocardial fibrosis. However, whether CMD in non-ischemic cardiomyopathy is a cause or an effect of the underlying cardiomyopathic process, or whether it can be potentially modifiable with specific therapies, remains incompletely understood.

Changes in the profile of NO synthases affect coronary blood flow autoregulation and myocardial contractile activity during restraint stress in rats.

The efficiency of autoregulation of the coronary blood flow and contractile activity of the myocardium in the presence of inhibitors of constitutive and inducible NO synthases was studied in rats exposed to 6-h restraint stress. Intracoronary administration of S-methylisothiourea (10 μmol/liter), but not L-NAME (60 μmol/liter) fully prevented post-stress increase in the volume coronary blood flow rate, intensity of heart perfusion, and reduction of ventricular developed pressure at all levels of perfusion pressure. Real-time PCR showed 6-fold increased expression of inducible NO-synthase mRNA in the heart tissue against the background of unchanged expression of neuronal and endothelial NO synthases and 2-3-fold elevated content of transcripts of stress-inducible genes Hspa1a and Hspbp1. It was shown that the hypotension of coronary vessels and reduced contractile function of the myocardium are related to NO production by inducible NO synthase in endotheliocytes of coronary vessels and cardiomyocytes.

Autoregulation of Coronary Blood Flow in the Isolated Beating Pig Heart

The isolated beating pig heart model is an accessible platform to investigate the coronary circulation in its truly morphological and physiological state, whereas its use is beneficial from a time, cost, and ethical perspective. However, whether the coronary autoregulation is still intact is not known. Here, we study the autoregulation of coronary blood flow in the working isolated pig heart in response to brief occlusions of the coronary artery, to step-wise changes in left ventricular loading conditions and contractile states, and to pharmacologic vasodilating stimuli. Six slaughterhouse pig hearts (473 ± 40 g) were isolated, prepared, and connected to an external circulatory system. Through coronary reperfusion and controlled cardiac loading, physiological cardiac performance was achieved. After release of a coronary occlusion, coronary blood flow rose rapidly to an equal (maximum) level as the flow during control beats, independent of the duration of occlusion. Moreover, a linear relation was found between coronary blood flow and coronary driving pressure for a wide variation of preload, afterload, and contractility. In addition, intracoronary administration of papaverine did not yield a transient increase in blood flow indicating the presence of maximum coronary hyperemia. Together, this indicates that the coronary circulation in the isolated beating pig heart is in a permanent state of maximum hyperemia. This makes the model excellently suitable for testing and validating cardiovascular devices (i.e., heart valves, stent grafts, and ventricular assist devices) under well-controlled circumstances, whereas it decreases the necessity of sacrificing large mammalians for performing classical animal experiments.

Direct Endoscopic Visual Assessment of a Transcatheter Aortic Valve Implantation and Performance in the PhysioHeart, an Isolated Working Heart Platform

Transcatheter aortic valve implantation (TAVI) is an increasingly considered option to treat aortic stenosis in patients with a high operative risk. Valve placement during the procedure is typically guided by angiography and/or echocardiography, whereas these techniques are also used to judge valvular function. More detailed postprocedure visualization may be obtained with 3-dimensional echocardiography or magnetic resonance imaging. These imaging methods appear to be adequate for clinical assessment of TAVI, but direct optical visualization with high temporal and spatial resolution would be advantageous to study the details of this new procedure. The working heart model as described by Chinchoy et al1 enables direct intracardiac endoscopy,2 which provides unique insights into the form, function, and physiology of the heart. We applied this approach to study the placement and performance …

Different Responses in Adult and Neonatal Hearts to Changes in Coronary Perfusion Pressure

The influence of coronary perfusion pressure on neonatal heart function has not been evaluated. We compared the coronary perfusion pressure-cardiac function relationship between neonatal and adult hearts. Neonatal and adult rabbit hearts were examined. The coronary perfusion pressure was changed in increments of 10 mmHg. Coronary blood flow and left ventricular functions were measured at each coronary perfusion pressure. Autoregulatory capacity for coronary blood flow was quantified by calculating the autoregulation index. In neonatal hearts, left ventricular developed pressure was decreased at high perfusion pressure, whereas in adult hearts left ventricular developed pressure increased at high perfusion pressure. In neonatal hearts, left ventricular enddiastolic pressure was elevated at both low and high perfusion pressure, whereas in adult hearts left ventricular enddiastolic pressure remained constant at all perfusion pressures. Adult hearts exhibited coronary blood flow autoregulation in the perfusion pressure range between 40 and 90 mmHg. In contrast, neonatal hearts did not show autoregulation in any perfusion pressure range. In neonatal hearts, both low and high perfusion pressure caused deterioration in ventricular function attributable to the immaturity of coronary autoregulatory capacity. We conclude that coronary perfusion pressure should be controlled within a narrow range for neonates.

An overview of radiotracers in nuclear cardiology

Coronary blood flow is regulated by anatomical, hydraulic, mechanical, and metabolic factors. 1 Myocardial perfusion depends on both the driving pressure gradient and the resistance of the vascular bed. Through autoregulation, the coronary bed maintains myocardial perfusion within a narrow range, despite wide fluctuations in coronary perfusion pressure. 2 Autoregulation of coronary blood flow is driven by changes in regional myocardial metabolism and oxygen consumption. Coronary artery stenosis may induce different alterations of the autoregulation of coronary blood flow, resulting in impairment in myocardial function such as myocardial ischemia, myocardial stunning, myocardial hibernation, and myocardial infarction. Different radiotracers may be used as means of assessing the impairment of myocardial function; the choice of which tracer must be used as a means of identifying this dysfunction should depend primarily on the clinical questions to be answered. Myocardial perfusion single-photon emission computed tomography (SPECT) with thallium-201‐ and technetium-99m‐labeled agents is a well-established modality for the evaluation of patients with suspected or known coronary artery disease (CAD).3-7 Furthermore, different positron emission tomography (PET) perfusion tracers may be used for the quantitative measurement of absolute or relative myocardial blood flow, such as nitrogen-13 ammonia, rubidium82 chloride, and oxygen-15 water. Moreover, considering that myocardial ischemia is associated with alterations in myocardial metabolism, the use of metabolic tracers has emerged as a useful approach in investigating the effects of CAD on myocardial metabolism. The tracers used as a means of assessing cardiac metabolism in patients with heart diseases are labeled fatty acids and fluorine-18 fluorodeoxyglucose (FDG). PERFUSION IMAGING AGENTS WITH SPECT Thallium-201

Myocardial perfusion during cardiopulmonary resuscitation (CPR): effects of 10, 25 and 50% coronary stenoses

Myocardial blood flow under normal physiologic conditions remains relatively unaltered by coronary lesions with diameter stenosis of less than 70%. However, during cardiac arrest and cardiopulmonary resuscitation (CPR), autoregulation of coronary blood flow is compromised. We studied the effect of previously considered ‘trivial’ coronary stenoses of 10, 25 and 50% on distal myocardial perfusion in 39 swine undergoing CPR for cardiac arrest. Endocardial blood flow distal to the stenosis was significantly less than that proximal in all the different stenoses groups (P<0.05). A 50% diameter stenosis also compromised epicardial blood flow distal to the stenosis (P<0.05). This study suggests that any coronary lesion may compromise myocardial perfusion during CPR. Since the vast majority of cardiac arrest victims have coronary artery disease, careful attention to maximizing myocardial blood flow during CPR is needed.

K+ATP channels and adenosine are not necessary for coronary autoregulation.

Autoregulation is defined as the intrinsic ability of an organ to maintain constant flow in the face of changing perfusion pressure. The present study evaluated the role of several potential mediators of coronary autoregulation: interstitial adenosine, ATP-sensitive K+ (K+ATP) channels, and myocardial oxygen and carbon dioxide tensions as reflected by coronary venous oxygen and carbon dioxide tensions. The left main coronary artery was cannulated, and blood was perfused at controlled pressures in closed-chest dogs. Interstitial adenosine concentration was estimated from arterial and venous adenosine concentrations with a previously described mathematical model. Autoregulation of coronary blood flow was observed between 100 and 60 mmHg. Glibenclamide, an inhibitor of K+ATP channels, reduced coronary blood flow by 19% at each perfusion pressure, but autoregulation was preserved. After stepwise reductions in coronary pressure to values > or = 70 mmHg, adenosine concentrations did not increase above basal levels. Adenosine concentration was elevated at 60 mmHg, suggesting a role for adenosine at the limit of coronary autoregulation. Adenosine is not required because glibenclamide, an inhibitor of adenosine-mediated vasodilation, did not reduce autoregulation or increase adenosine concentration. Coronary venous oxygen and carbon dioxide tensions were little changed during autoregulation before the inhibition of K+ATP channels and adenosine vasodilation with glibenclamide. However, coronary venous carbon dioxide tension rose progressively with decreasing coronary pressure after glibenclamide. The increase in carbon dioxide indirectly suggests that carbon dioxide-mediated vasodilation compensated for the loss of K+ATP-channel function. In summary, neither K+ATP channels nor adenosine is necessary to maintain coronary flow in the autoregulatory range of coronary arterial pressure from 100 to 60 mmHg.

Fluxo coronário desregulado durante reperfusão pós cardioplegia

Metabolic coronary blood flow recruitment and distribution were studied in the setting of ventricular fibrillation (VF) during post-cardioplegia reperfusion. Fifteen pigs were placed on cardiopulmonary bypass and subjected to one hour of intermittent cold blood antegrade cardioplegia, followed by controlled myocardial reperfusion. According to the electromechanical status during the first ten minutes of reperfusion, the animals were allocated into 3 groups (n=5). Whereas Group 1 remained asystolic, the other two groups developed short (Group 2) or long duration VF (Group 3). Myocardial oxygen consumption (MVO2), in m/O2 /min/g (mean ± standard error) during reperfusion was 1.325 ± 0.144 (Group 1); 2.472 ± 0.208 (Group 2) and, 2.469 ± 0.228 (Group 3). MVO2 difference between asystolic and both short and long duration VF hearts was significant (p<0.001). Groups 1.2 and 3 endo-epi ratio and global coronary blood flow rate (169.3 ± 11.7; 185.0 ± 15.7 and 179.9 ± 13.2 ml/min/100g; respectively) were similar. These results demonstrate that coronary blood flow autoregulation was impaired because there was no increase in myocardial perfusion in response to the increase oxygen consumption imposed by VF during the first ten minutes of post cryocardioplegia reperfusion. This finding is of great clinical importance because it suggests that VF can potentially aggravate reperfusion lesions in formerly compromised hearts, i.e., those with coronary artery obstruction, ventricular distension or ventricular hypertrophy.

Blockade of Adenosine Triphosphate-sensitive Potassium Channels Eliminates Isoflurane-induced Coronary Artery Vasodilation

The mechanisms by which volatile anesthetics induce vasodilation are unknown. Recent studies of adenosine triphosphate-sensitive potassium channels (KATP channels) in the vascular smooth muscle of the coronary circulation suggest that these channels play a role in the coronary artery dilation produced by hypoxemia, the coronary blood flow (CBF) reactive hyperemic response, and in CBF auto regulation. We therefore conducted this study to determine the role of KATP channels in isoflurane-induced coronary vasodilation. Studies were conducted in six open-chest, anesthetized swine. The left anterior descending coronary artery was cannulated and perfused by blood passed through a membrane oxygenator. This preparation allowed us to administer drugs and volatile anesthetics regionally to the perfused myocardium, minimizing systemic effects. Regional CBF response to 1.5% and 3.0% isoflurane administered via the membrane oxygenator was measured before and after blockade of KATP channels, and was compared to the vasodilation produced by regional administration of several doses of sodium nitroprusside and adenosine. Blockade of KATP channels was achieved by regional intracoronary administration of glibenclamide (1-22 micrograms.kg-1.min-1), a specific blocker of these channels. Administration of 1.5 and 3.0 percent isoflurane increased regional CBF by 29 +/- 29% and by 62 +/- 28%, respectively. Under control conditions, blockade of KATP channels decreased mean CBF by 18%, but did not cause ischemia. KATP channel blockade totally eliminated the vasodilator response to both doses of isoflurane. During KATP channel blockade the response to 3% isoflurane was converted to net vasoconstriction: mean delta CBF = -5% +/- 6%, P = < 0.05 versus control. Negative inotropic effects of isoflurane were not eliminated by glibenclamide. Because KATP channel blockade was so effective in eliminating isoflurane-induced coronary vasodilation, the dose of glibenclamide was decreased in sequential experiments, but total blockade of isoflurane vasodilation was achieved even at the smallest dose of glibenclamide studied (1 microgram.kg-1.min-1). The vasodilator response to nitroprusside was not affected, and the vasodilator response to adenosine was partially inhibited (consistent with their known mechanisms of action). Blockade of KATP channels by glibenclamide completely inhibits isoflurane-induced coronary vasodilation in the regionally perfused swine myocardium. The response to sodium nitroprusside, a drug that induces vasodilation via a different mechanism, was unaffected. The response to adenosine, a drug whose vasodilation is partially mediated via KATP channels, was partially inhibited. These results suggest that in vivo isoflurane-induced coronary artery vasodilation is predominantly mediated by KATP channels.

Coronary Blood Flow Autoregulation and Flow Heterogeneity in the Stunned Heart.

We used an anesthetized swine model of regionally "stunned" myocardium to determine the effect of stunning on coronary autoregulation and blood flow heterogeneity. In 18 domestic swine, stunning was accomplished by reducing blood flow to the left anterior descending coronary artery (LAD) by approximately 75% of baseline for 15 min and restoring it to normal for 1 hour. We quantified coronary autoregulation using both the slope of coronary pressure-flow curves and an autoregulation index. We quantified blood flow heterogeneity using radioactive microspheres to determine the variability in flow (dispersion index) among forty 200 mg segments of myocardium from the center of the stunned, LAD-perfused left ventricle. Before and after stunning, we measured autoregulation, myocardial blood flow and flow heterogeneity, as well as hemodynamic indices of myocardial oxygen demand. Fifteen min of ischemia and 1 hour of reperfusion produced both a 46% reduction in mechanical function, and a 7% drop in systemic arterial pressure, but not change in heart rate or rate pressure product. Myocardial oxygen consumption was 15% reduced and myocardial blood flow 16% reduced in the stunned myocardium when measured at one hour of reperfusion. Fifteen min after reperfusion, the slope of the coronary pressure flow plots and the coronary venous oxygenation were increased whereas the autoregulation index decreased. These findings all indicate reduced autoregulation during early reperfusion. However, after one hour of reperfusion, the slope of the coronary pressure-flow relation (0.41 +/- 0.19 vs. 0.48 +/- 0.26 ml.100 g-1.min-1.mmHg-1) and the autoregulation index (0.43 +/- 0.16 vs. 0.30 +/- 0.32) were unchanged from control measurements (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoregulation of coronary blood flow in isolated rat heart after NO-synthase blockade

Autoregulation of coronary blood flow in isolated rat heart after NO-synthase blockade

Effect of transient coronary occlusion on coronary blood flow autoregulation, vasodilator reserve and response to adenosine in the dog

Myocardial ischemia of short duration (15 to 20 min) produces myocardial “stunning” during reperfusion. The vasoregulatory and contractile status of reperfuscd myocardium during normal and reduced perfusion pressures is of interest in the treatment of patients with unstable angina. In the present study the effects of 15 min of reversible ischemic injury on several aspects of coronary vasoregulation were assessed with use of pressure-flow curves in anesthetized open chest dogs. The left anterior descending coronary artery was cannulated and perfused with arterial blood with use of a servo-controlled roller pump. The autoregulatory gain and an adenosine dose-response curve for coronary flow before and after ischemia and reperfusion were obtained.The maximal autoregulatory gain values in the pressure range of 140 to 60 mm Hg were not significantly different before and after ischemia and reperfusion (0.41 ± 0.08 vs. 0.5 ± 0.06, p > 0.1). The adenosine dose-response curve was significantly shifted to the right after reperfusion; however, coronary blood flows during maximal adenosine vasodilation over a large range of perfusion pressures (140 to 60 mm Hg) were significantly greater after ischemia and reperfusion. The pressure-dependent decrease in segment shortening (sonomicrometry) over the coronary pressure range of 160 to 30 mm Hg was similar in myocardium before and after stunning. Contractile function in the stunned myocardium at normal (100 mm Hg) and low (40 mm Hg) coronary perfusion pressures was similarly and significantly enhanced by the administration of adenosine.It is concluded that 1) coronary autoregulation is unchanged after brief ischemia and reperfusion; 2) although maximal coronary vascular conductance assessed with adenosine is greater after ischemia, the coronary circulation shows a demised coronary sensitivity to exogenous adenosine; 3) the relation of contractile function to coronary pressure before and after stunning is unchanged; and 4) enhancement of function in stunned myocardium by vasodilation with adenosine occurs at low and normal perfusion pressures.

Myogenic activity in isolated subepicardial and subendocardial coronary arterioles

The goal of this study was to examine myogenic responses of isolated porcine subepicardial and subendocardial arterioles (80-100 micron in diameter) within physiological ranges of intraluminal pressure. Arterioles were located by perfusion with india ink-gelatin solution then dissected and cannulated with glass micropipettes. Intraluminal pressure was altered in 20-cmH2O steps over the range of 20-140 cmH2O. IN physiological salt solution (36-37 degrees C), the coronary arterioles developed spontaneous tone and exhibited myogenic responses. At the lower pressures (20-60 cmH2O), subendocardial arterioles responded passively (diameter decreased from a control diameter at 60 cmH2O), whereas subepicardial arterioles maintained their diameters. At higher pressures (100-140 cmH2O), both subepicardial and subendocardial arterioles demonstrated myogenic constriction, but subepicardial arterioles demonstrated greater myogenic constriction than subendocardial arterioles. This implies that myogenic autoregulation in subepicardial arterioles is better than that in the subendocardial arterioles at both low and high pressures. In the presence of nitroprusside (10(-4) M), all arterioles responded to pressure changes passively, and there were no differences between subepicardial and subendocardial vessels. The functional integrity of the endothelium was verified by relaxation to substance P (10(-7) M). This is the first in vitro study to demonstrate coronary myogenic activity and transmural differences in these arteriolar responses. Our data support the concept that myogenic mechanisms in 80 to 100-micron arterioles may actively contribute to autoregulation of coronary blood flow.

Surface-induced hypothermia: Effects on coronary blood flow autoregulation and vascular reserve

Surface-induced hypothermia has been shown to exert a protective effect in canine models of myocardial infarction. However, its effects on coronary blood flow (CBF) autoregulation and coronary vascular reserve (CVR) have not been investigated. The effects of mild (32°C) and moderate (27°C) hypothermia on CBF autoregulation and CVR (at 60 mm Hg diastolic pressure) were studied using a chronically instrumented canine preparation. Coronary artery pressure-flow relations were obtained over a wide range of coronary diastolic pressures (10 to 106 mm Hg) with autoregulation intact and during adenosine-induced maximal coronary conductance (MCC) at 37, 32, 27°C ( n = 7 dogs), and after rewarming ( n = 5 dogs). Halothane (1 MAC end-tidal concentration, temperature adjusted) was the anesthetic. Autoregulation remained intact during hypothermia. CBF remained relatively constant between diastolic pressures of 43.1 ± 9.0 and 84.0 ± 14.4 mm Hg (mean ± SD). No significant differences were observed between temperatures in the autoregulated pressure range. CBF correlated well with myocardial oxygen consumption (MVO 2) ( r 2 = 0.81, P < 0.0001). There were no significant changes in MVO 2, CBF, MCC, or CVR at 32°C. At 27°C, MVO 2(3.65 ± 1.3 at 37°C vs 2.35 ± 1.4 ml O 2 · min −1 at 27°C), autoregulated CBF (34.9 ± 15.1 vs 19.5 ± 10.8 ml · min −1), the slope of the line of MCC (4.31 ± 0.7 vs 2.7 ± 0.4 ml · mm −1 · min −1), and CVR (147.1 ± 24.6 vs 90.1 ± 27.3 ml · min −1) were all less than control ( P < 0.05). After rewarming to 37°C, no significant changes from control were noted. The authors conclude that coronary autoregulation remains intact at both 32 and 27°C, although MCC and CVR are significantly decreased at 27°C.

Effects of halothane, enflurane, and isoflurane on coronary blood flow autoregulation and coronary vascular reserve in the canine heart.

To investigate the effects of volatile anesthetics on coronary blood flow (CBF) autoregulation and coronary vascular reserve, studies were performed on chronically instrumented dogs, awake and during the administration of 1.0 MAC halothane, enflurane, and isoflurane. Coronary pressure-flow plots were generated by measuring left anterior descending coronary artery blood flow while varying coronary inflow pressure with a hydraulic occluder. Autoregulation was quantitated by two measures: the slope of the horizontal "autoregulated" portion of the pressure-flow relationship and the autoregulation index (ArI) of Norris. Slope values (ml.min-1.mmHg-1 +/- SD) were: awake, 0.243 +/- 0.043; halothane, 0.414 +/- 0.044; enflurane, 0.587 +/- 0.187; and isoflurane, 0.795 +/- 0.246. The increase in slope was statistically significant only for halothane and isoflurane (P less than .05). The ArI approaches 1.0 when autoregulation is perfect, and approaches zero or is a negative number when autoregulation is absent. The authors found ArI values of: awake, 0.55; halothane, -0.08; enflurane, -0.01; isoflurane, -0.02. These values indicate good autoregulation while awake, but impaired autoregulation with all three anesthetics (P less than .05). Coronary vascular reserve was calculated, at a diastolic coronary pressure of 40 mmHg, as the difference between resting flow and flow during maximal coronary vasodilation induced by intracoronary adenosine. Coronary vascular reserve, maximal coronary conductance, and coronary zero-flow pressure were not significantly altered by these anesthetics. The authors conclude that 1.0 MAC enflurane, halothane, and isoflurane mildly disrupt CBF autoregulation, increasing CBF out of proportion to myocardial demands. Under the conditions of this study, these anesthetics do not affect maximal CBF or coronary vascular reserve.

Transmural variation in autoregulation of coronary blood flow in hyperperfused canine myocardium.

Transmural variation in autoregulation of coronary blood flow in hyperperfused canine myocardium.

Indomethacin and the prostaglandin hypothesis of coronary blood flow regulation.

1. Recent experimental data support the view that prostaglandins might be involved in autoregulation of coronary blood flow. Since indomethacin blocks prostaglandin synthesis, the present study was performed to determine whether indomethacin also inhibits coronary vasodilatation induced by hypoxia.2. Coronary and systemic haemodynamic and metabolic effects of hypoxia (5% and 8% oxygen in nitrogen) were studied in intact, anaesthetized and vagotomized dogs before and after indomethacin.3. 30 and 60 min after administration of indomethacin coronary blood flow increases produced by hypoxia were considerably lower than those before indomethacin.4. These results are held to lend support to the hypothesis that prostaglandins are involved in the autoregulation of coronary blood flow.

A nomogram relating pO2, pH, temperature, and hemoglobin saturation in the dog.

Abstract : The data from 591 dog blood samples on which observations were made of Po sub 2, hemoglobin saturation, Pco sub 2, pH, and temperature were analyzed by means of a digital computer. The Hill equation was found to fit the data well in the range from 20% to 98% saturation. Linear terms for pH and temperature effects were found to improve appreciably the prediction ability of the equation. A similar term for Pco sub 2, although statistically significant, did not contribute enough additional precision in prediction to justify its inclusion in the final equations. The equations derived are: log (S/1-S) = 2.5198 log Po sub 2 + 1.1804 (pH-7.0) - .047234T - 2.3621 and log Po sub 2 = .37143 log (S/1-S) - .48047 (pH-7.0) + .019518T + .92247. A nomogram relating these variables is also presented. (Author)