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

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00689.2017 ◽

2018 ◽

Vol 315 (1) ◽

pp. H132-H140 ◽

Cited By ~ 1

Author(s):

Tyler D. Vermeulen ◽

Lindsey M. Boulet ◽

Mike Stembridge ◽

Alexandra M. Williams ◽

James D. Anholm ◽

...

Keyword(s):

Coronary Artery ◽

Adrenergic Receptor ◽

Blood Velocity ◽

Rate Pressure Product ◽

Receptor Blockade ◽

Vascular Response ◽

Arterial Blood ◽

Hypercapnic Hypoxia ◽

The Mean ◽

Adrenergic Receptor Blockade

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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Renin, aldosterone and arterial pressure responses to acute β-adrenergic receptor blockade in hypertensive patients

Klinische Wochenschrift ◽

10.1007/bf01614294 ◽

1976 ◽

Vol 54 (16) ◽

pp. 775-782 ◽

Cited By ~ 2

Author(s):

K. O. Stumpe ◽

R. Kolloch ◽

W. Gramann ◽

H. Vetter ◽

Ch. Ressel ◽

...

Keyword(s):

Arterial Pressure ◽

Adrenergic Receptor ◽

Receptor Blockade ◽

Hypertensive Patients ◽

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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Effects of alpha-adrenergic receptor blockade on coronary circulation in conscious dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1982.243.1.h94 ◽

1982 ◽

Vol 243 (1) ◽

pp. H94-H98

Author(s):

P. Macho ◽

T. H. Hintze ◽

S. F. Vatner

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Adrenergic Receptor ◽

Coronary Circulation ◽

Conscious Dogs ◽

Receptor Blockade ◽

Receptor Blocking ◽

Blocking Agents ◽

Alpha Adrenergic Receptor ◽

Adrenergic Receptor Blockade

The effects of three alpha-adrenergic-receptor blocking agents (phentolamine, prazosin, and trimazosin) were compared on the coronary circulation and left ventricular (LV) function in chronically instrumented conscious dogs. The three alpha-adrenergic-receptor blocking agents were administered in equidepressor doses (mean arterial pressure fell by approximately 20%) and in the presence of beta-adrenergic-receptor blockade and constant heart rate. LV systolic pressure, LV end-diastolic pressure, and LV end-diastolic diameter also fell similarly with the three drugs. Phentolamine decreased the time rate of change of LV pressure (LV dP/dt) by 21 +/- 3%, whereas trimazosin and prazosin decreased LV dP/dt only by 14 +/- 2 and 11 +/- 2%, respectively. LV velocity was not changed with trimazosin and prazosin but decreased with phentolamine by 12 +/- 4%. The three drugs exerted differential effects on the coronary circulation. Only trimazosin increased coronary blood flow (18 +/- 5%). Trimazosin decreased late diastolic coronary resistance (LDCR) by 35 +/- 2%, which was significantly more than reductions in LDCR induced by prazosin (22 +/- 2%) and by phentolamine (11 +/- 3%). A test dose of phenylephrine (5.0 micrograms/kg) increased mean arterial pressure by 53 +/- 3.5 mmHg. After trimazosin, prazosin, and phentolamine, the same dose of phenylephrine increased mean arterial pressure by 24 +/- 2.1, 14 +/- 1.6, and 1.9 +/- 0.6 mmHg, respectively. The response after phentolamine was significantly less than with trimazosin (P less than 0.01) and prazosin (P less than 0.02). Thus the capacity of these three alpha-adrenergic-receptor blocking drugs to dilate coronary vessels is inversely proportional to their capability to block exogenous alpha-adrenergic-receptor agonists.

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T5 spinal cord transection increases susceptibility to reperfusion-induced ventricular tachycardia by enhancing sympathetic activity in conscious rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01019.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. H3333-H3339 ◽

Cited By ~ 27

Author(s):

Heidi L. Lujan ◽

Stephen E. DiCarlo

Keyword(s):

Spinal Cord ◽

Ventricular Tachycardia ◽

Coronary Artery ◽

Cause Of Death ◽

Adrenergic Receptor ◽

Sympathetic Activity ◽

Left Main Coronary Artery ◽

Sustained Ventricular Tachycardia ◽

Spinal Cord Transection ◽

Left Main

We recently documented that paraplegia (T5 spinal cord transection) alters cardiac electrophysiology and increases the susceptibility to ventricular tachyarrhythmias induced by programmed electrical stimulation. However, coronary artery occlusion is the leading cause of death in industrially developed countries and will be the major cause of death in the world by the year 2020. The majority of these deaths result from tachyarrhythmias that culminate in ventricular fibrillation. β-Adrenergic receptor antagonists have been shown to reduce the incidence of sudden cardiac death. Therefore, we tested the hypothesis that chronic T5 spinal cord transection increases the susceptibility to clinically relevant ischemia-reperfusion-induced sustained ventricular tachycardia due to enhanced sympathetic activity. Intact and chronic (4 wk after transection) T5 spinal cord-transected (T5X) male rats were instrumented to record arterial pressure, body temperature, and ECG. In addition, a snare was placed around the left main coronary artery. The susceptibility to sustained ventricular tachycardia produced by 2.5 min of occlusion and reperfusion of the left main coronary artery was determined in conscious rats by pulling on the snare. Reperfusion culminated in sustained ventricular tachycardia in 100% of T5X rats (susceptible T5X, 10 of 10) and 0% of intact rats [susceptible intact, 0 of 10 ( P < 0.05, T5X vs. intact)]. β-Adrenergic receptor blockade prevented reperfusion-induced sustained ventricular tachycardia in T5X rats [susceptible T5X 0 of 8, 0% ( P < 0.05)]. Thus paraplegia increases the susceptibility to reperfusion-induced sustained ventricular tachycardia due to enhanced sympathetic activity.

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