Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po2 and Pco2 or if coronary vascular responses are the result of concomitant increases in myocardial O2 consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po2 and Pco2 would be attenuated in healthy men when [Formula: see text] was attenuated with β1-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β1-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LADV; Doppler echocardiography), heart rate, and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (MELV) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, MELV, and LADV, but only RPP and MELV were attenuated (4–18%) after β1-adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and MELV responses, β1-adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β1-adrenergic receptor blockade. These results indicate a direct influence of arterial Po2 on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β1-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O2 demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O2 consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β1-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po2 and Pco2 during hypercapnic hypoxia.

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Sex influences the susceptibility to reperfusion-induced sustained ventricular tachycardia and β-adrenergic receptor blockade in conscious rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00596.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. H2799-H2808 ◽

Cited By ~ 14

Author(s):

Heidi L. Lujan ◽

Victoria J. Kramer ◽

Stephen E. DiCarlo

Keyword(s):

Ventricular Tachycardia ◽

Coronary Artery ◽

Adrenergic Receptor ◽

Left Main Coronary Artery ◽

Gonadal Hormones ◽

Receptor Blockade ◽

Left Main ◽

Reperfusion Arrhythmias ◽

Conscious Rats ◽

Adrenergic Receptor Blockade

Reperfusion after a brief period of cardiac ischemia can lead to potentially lethal arrhythmias. Importantly, there are sex-related differences in cardiac physiology and in the types and severity of cardiac arrhythmias. Therefore, we tested the hypothesis that gonadal hormones influence the susceptibility to reperfusion-induced sustained ventricular tachycardia (VT), as well as the response to β-adrenergic receptor blockade. Male and female intact and gonadectomized rats were instrumented, and arterial pressure, temperature, ECG, and cardiac output were recorded. In addition, a snare was placed around the left main coronary artery. Tension was applied to the snare for determination of susceptibility to sustained VT produced by 3 min of occlusion and reperfusion of the left main coronary artery in conscious rats. Reperfusion culminated in sustained VT in 77% (10 of 13 susceptible) of female rats and 56% (9 of 16 susceptible) of male rats ( P > 0.05, male vs. female). β-Adrenergic receptor blockade prevented sustained VT in females only [1 of 9 susceptible females (11%) vs. 6 of 9 susceptible males (67%), P < 0.05]. Ovariectomy did not significantly reduce the susceptibility to reperfusion arrhythmias [5 of 9 susceptible (56%)]. In sharp contrast, orchidectomy significantly increased the susceptibility to reperfusion arrhythmias [9 of 9 susceptible (100%)]. Finally, β-adrenergic receptor blockade prevented sustained VT in ovariectomized females [0 of 4 susceptible (0%)] and orchidectomized males [0 of 7 susceptible (0%)], but the protective effect of β-blockade was due to a reduction in heart rate in males only. Thus gonadal hormones influence the susceptibility to reperfusion-induced arrhythmias, as well as the effects and mechanisms of β-adrenergic receptor blockade.

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The mechanism of beta-adrenergic receptor blockade-induced elevation of arterial blood pressure in rats

Archives Internationales de Physiologie et de Biochimie ◽

10.3109/13813458209070568 ◽

1982 ◽

Vol 90 (3) ◽

pp. 173-178 ◽

Cited By ~ 1

Author(s):

F. Charocopos

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Adrenergic Receptor ◽

Receptor Blockade ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Arterial Blood ◽

Adrenergic Receptor Blockade

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Beta-adrenergic receptor blockade attenuates the electronic uncoupling induced by coronary artery occlusion

Computers in Cardiology, 2004 ◽

10.1109/cic.2004.1442958 ◽

2005 ◽

Author(s):

C.L. del Rio ◽

R. Dzwonczyk ◽

P.I. McConnell ◽

B.D. Clymer ◽

M.B. Howie ◽

...

Keyword(s):

Coronary Artery ◽

Adrenergic Receptor ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Receptor Blockade ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Adrenergic Receptor Blockade

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Sex differences to myocardial ischemia and β-adrenergic receptor blockade in conscious rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01241.2007 ◽

2008 ◽

Vol 294 (4) ◽

pp. H1523-H1529 ◽

Cited By ~ 15

Author(s):

Heidi L. Lujan ◽

Stephen E. DiCarlo

Keyword(s):

Sex Differences ◽

Ventricular Tachycardia ◽

Coronary Artery ◽

Arterial Pressure ◽

Adrenergic Receptor ◽

Gonadal Hormones ◽

Sustained Ventricular Tachycardia ◽

Receptor Blockade ◽

Conscious Rats ◽

Adrenergic Receptor Blockade

We recently documented sex differences in the susceptibility to reperfusion-induced sustained ventricular tachycardia and β-adrenergic receptor blockade in conscious rats. However, the effect of sex on ischemia-induced ventricular arrhythmias and β-adrenergic receptor blockade is underinvestigated. Therefore, we tested the hypothesis that gonadal hormones influence the ventricular arrhythmia threshold (VAT) induced by coronary artery occlusion as well as the response to β-adrenergic receptor blockade. The VAT was defined as the time from coronary occlusion to sustained ventricular tachycardia resulting in a reduction in arterial pressure. Male and female intact and gonadectomized (GnX) rats were instrumented with a radiotelemetry device for recording arterial pressure, temperature, and ECG, as well as a Doppler ultrasonic flow probe to measure cardiac output and a snare around the left main coronary artery. The VAT was determined in conscious rats by pulling on the snare. The VAT was significantly longer in intact females (5.56 ± 0.19) vs. intact males (4.31 ± 0.14 min). This sex difference was abolished by GnX. Specifically, GnX decreased the VAT in females (4.55 ± 0.22) and increased the VAT in males (5.14 ± 0.30 min). Thus male sex hormones increase and female sex hormones decrease the susceptibility to ischemia-induced sustained ventricular tachycardia. β-Adrenergic receptor blockade increased the VAT in intact males and GnX females only. Thus gonadal hormones influence the response to β-adrenergic receptor blockade. Uncovering major differences between males and females in the pathophysiology of the cardiovascular system may result in sex-specific optimization of patient treatments.

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Adrenergic stimulation and blockade in colonic circulation of the rhesus monkey

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1981.240.1.g25 ◽

1981 ◽

Vol 240 (1) ◽

pp. G25-G31

Author(s):

J. C. Kerr ◽

K. G. Swan

Keyword(s):

Adrenergic Receptor ◽

Arterial Blood Flow ◽

Receptor Blockade ◽

Adrenergic Stimulation ◽

Beta Adrenergic Receptor ◽

Receptor Stimulation ◽

Beta Adrenergic ◽

Alpha Adrenergic Receptor ◽

Arterial Blood ◽

Adrenergic Receptor Blockade

Adrenergic stimulation and blockade on inferior mesenteric arterial blood flow (Q) were measured in anesthetized rhesus monkeys. Control Q was 25 +/- 2 (mean +/- SE) ml/min; aortic and portal venous pressures were 121 +/- 5 and 6.5 +/- 1.0 mmHg. Calculated inferior mesenteric arterial resistance was 5.10 +/- 0.42 peripheral resistance units. Norepinephrine (N), 10(-3) to 1.0 microgram/kg intra-arterially, caused dose-dependent decreases in Q. Epinephrine (E) increased Q at 10(-3) microgram/kg in 60% of the animals studied and decreased Q at the higher doses (10(-2) to 1.0 microgram/kg). Isoproterenol (I) increased Q at all four doses studied. Ten-minute infusions of N and E (0.5 microgram x kg-1 x min-1) caused sustained decreases, and I caused sustained increases in Q. Autoregulatory escape was not observed. alpha-Adrenergic receptor blockade (phenoxybenzamine) attenuated the vasoconstrictor responses to N, but did not "reverse" the vasoconstrictor response to E (vasodilation). beta-adrenergic receptor blockade (propranolol) attenuated the vasodilator responses to I, but did not alter significantly the responses to E or N. These data indicate that in the monkey colonic circulation, alpha-adrenergic receptor stimulation causes vasoconstriction and beta-adrenergic receptor stimulation causes vasodilation.

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Contribution of Hypercapnia and Hypoxia to the Vascular Response to Ischaemia

Clinical Science ◽

10.1042/cs0390203 ◽

1970 ◽

Vol 39 (2) ◽

pp. 203-222 ◽

Cited By ~ 7

Author(s):

H. A. Kontos ◽

D. W. Richardson ◽

A. J. Raper ◽

J. L. Patterson

Keyword(s):

Adrenergic Receptor ◽

Circulatory Arrest ◽

Venous Blood ◽

Receptor Blockade ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Air Breathing ◽

Vasodilator Response ◽

Arterial Blood ◽

Adrenergic Receptor Blockade

1. Hypoxia, induced by 7–12% oxygen breathing, produced vasodilatation in the intact or in the phenoxybenzamine and propranolol treated forearm of human volunteers when arterial blood PO2 decreased below 45 mmHg, or when deep forearm venous blood PO2 decreased below 35–40 mmHg. 2. Circulatory arrest of the forearm following alpha and beta adrenergic receptor blockade was followed by greater increases in blood flow and greater decreases in forearm vascular resistance during CO2 breathing than during room air breathing. The increased flow following ischaemia was maintained at a high level until CO2 administration was stopped. 3. The vasodilator response following ischaemia of the human forearm, produced by digital occlusion of the brachial artery, was compared to that produced by hypercapnia or hypoxia or a combination of the two, produced by breathing the appropriate gas mixtures. The forearm was pre-treated with phenoxybenzamine and propranolol to produce alpha and beta adrenergic receptor blockade. For equal increases in deep forearm venous blood PCO2 the vasodilator response to hypercapnia averaged 60% of that following ischaemia. For equal decreases in deep forearm venous blood PO2 the vasodilator response to hypoxia averaged 26% of that produced by ischaemia. The vasodilator response to ischaemia was not modified by breathing 100% oxygen to maintain the deep forearm venous blood PO2 at a level above that seen with the circulation free during room air breathing. Combined hypoxia and hypercapnia of equal severity as those produced by ischaemia resulted in a vasodilator response which averaged 64% of that produced by ischaemia.

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