Epicardial Cross-sectional Area Research Articles

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Dehydroepiandrosterone Sulfate Induces Acute Vasodilation of Porcine Coronary Arteries In Vitro and In Vivo

Although an inverse relationship between dehydroepiandrosterone sulfate (DHEAS) and coronary artery disease has been demonstrated in men, the vascular effects of DHEAS are not well defined. The vasoactive effects of intracoronary DHEAS and testosterone (0.1 nM to 1 microM) were examined in vivo in 24 pigs. Epicardial cross-sectional area was measured by intravascular ultrasound, and coronary flow velocity by intravascular Doppler velocimetry. We also examined the effects of antagonism of the androgen receptor, nitric oxide synthase, and potassium channels on DHEAS-induced vasodilation in vitro in coronary rings from male and female pig hearts. DHEAS and testosterone induced increases in cross-sectional area, average peak velocity, and coronary blood flow. The maximal increase in coronary blood flow in response to testosterone was 1.26-fold (P=0.02), and in average peak velocity 1.43-fold (P=0.05), greater than that to DHEAS, whereas increases in cross-sectional area were similar. Vasodilation to both hormones was rapid, with maximal responses occurring <10 minutes after administration. In vitro, DHEAS and testosterone induced vasodilation in coronary rings, greater with testosterone. At doses of 0.1 and 1 microM, the vasodilator effects of DHEAS and testosterone were inhibited by the androgen receptor antagonist flutamide but not the estrogen receptor antagonist ICI 182,780. At 10 microM, neither DHEAS- nor testosterone-induced vasorelaxation was inhibited by flutamide, ICI 182,780, L-NAME, or deendothelialization, but both were attenuated by pretreatment with glibenclamide. No gender differences were observed in any of the responses examined. In conclusion, DHEAS is an acute coronary artery vasodilator, but less potent than testosterone. Its effect might be mediated via androgen receptors and may involve ATP-sensitive potassium channels.

Ventricular-vascular uncoupling by acute conotruncal occlusion in the stage 21 chick embryo.

Embryonic ventricular diastolic and systolic function was evaluated during normal ejection (coupled) and during acute ventricular outflow tract occlusion (uncoupled) in the stage 21 chick embryo. We simultaneously measured ventricular pressure with a servo-null system and ventricular dimensions using video microscopy. Experimental protocols included 1) baseline recording followed by acute conotruncal (CT) ligation (n = 15) and 2) baseline recording, preload increase using Krebs-Henseleit buffer (3 microliters), preload reduction via venous hemorrhage, and then CT occlusion (n = 20). Ventricular epicardial cross-sectional area was converted to internal volume using wall volume measures and assuming an ellipsoid geometry to produce pressure-volume loops. We calculated the time constant of ventricular pressure decline using a monoexponential decay function with a pressure asymptote. As previously noted, heart rate was unaffected by acutely altered preload or afterload. CT ligation increased end-systolic pressure, maximal +dP/dt, and the time constant of ventricular pressure decline and decreased stroke volume indexed for end-diastolic volume. Thus the embryonic ventricle has significant contractile reserve masked in vivo by the dynamic coupling between the ventricle and arterial circulation.

Coronary vasodilation induced by angiotensin-converting enzyme inhibition in vivo: differential contribution of nitric oxide and bradykinin in conductance and resistance arteries.

We studied in coronary conductance and resistance arteries the coronary vasodilator effects of the angiotensin-converting enzyme inhibitor ramiprilat and the contribution of nitric oxide, bradykinin, and prostaglandins to this vasodilation. In seven anesthetized dogs, a Doppler guidewire was placed in the circumflex coronary artery to measure coronary flow velocity, and an ultrasound imaging catheter was introduced over the Doppler wire to measure coronary cross-sectional area. Drugs were infused directly into the left main coronary artery to minimize systemic effects. Ramiprilat increased both epicardial cross-sectional area and coronary blood flow velocity, resulting in an increase in absolute coronary blood flow. Pretreatment with N omega-nitro-L-arginine methyl ester (100 micromol/L intracoronary) to block nitric oxide synthase attenuated ramiprilat-induced increase in epicardial coronary cross-sectional area (P<.05) but not in coronary flow velocity or coronary blood flow. In contrast, pretreatment with the selective bradykinin antagonist HOE 140 (10 micromol/L) attenuated ramiprilat-induced increase in flow velocity (P<.025) and coronary blood flow (P<.05) but not epicardial coronary cross-sectional area. Pretreatment with indomethacin (5 mg/kg body wt IV) did not alter ramiprilat-induced increase in epicardial cross-sectional area, nor did it significantly influence coronary blood flow. Other than decreasing angiotensin II production, acute ramiprilat-induced vasodilation in canine coronary conductance arteries is mediated in part by nitric oxide. Ramiprilat-induced vasodilation in resistance arteries is in part mediated by the action of bradykinin.

901-116 Coronary Vascular Relaxation Induced by Testosterone In Vivo is Gender Independent

To assess coronary vasoreactive response of testosterone and its relation to gender, we examined the effect of intracoronary testosterone (10 -10 to 10 -6 M) on epicardial and resistance coronary arteries in vivo in both male (5) and female (5) dogs. Changes in average peak flow velocity (APV) were assessed using a 0.014” Doppler guidewire (Cardiometrics), and epicardial cross-sectional area (CSA) was measured using a 4.3 F, 30 MHz ultrasound imaging catheter (CVIS). Guidewire and imaging catheter were positioned in the left circumflex artery. Testosterone induced a significant increase in both CSA, APV and calculated volumetric coronary blood flow (CBFI at the 10 -7 and 10 -6 M concentrations (CSA: 15.2 ± 10.2% increase at 10 -6 M (p = 0.05); APV: 36.4 ± 12.8 increase at 10 -7 (p &lt; 0,01) and 73.8 ± 66.8% increase at 10- 6 M (p = 0.004); CBF: 205% increase at 10 -6 M (p = 0.04)). Coronary vasorelaxation was equal in both males and females. No significant changes in heart rate or systemic pressure were noted. We conclude that acute testosterone administration induces epicardial and resistance coronary artery dilation in vivo and coronary vasorelaxation is independent of gender.

901–39 Testosterone-induced Coronary Conductance and Resistance Vessel Relaxation In Vivo: Potential Mechanisms of Action

Although testostone causes relaxation of the coronary vascular bed, its mechanisms of action has not been defined. We examined the effect of in-tracoronary testosterone (10 -6 to 10 -5 M) on epicardial and resistance coronary arteries in vivo in 10 dogs (5 male, 5 female). Changes in coronary average peak velocity (APV) were assessed using a 0.014” Doppler guidewire (Cardiometrics), and epicardial cross-sectional area (CSA) was measured using a 4.3F, 30 MHz ultrasound imaging catheter (CVIS). After establishing a baseline response, the contribution of nitric oxide (NO), prostaglandins and ATP-sensitive K + channels was assessed. Testosterone induced a significant increase in both CSA and APV at the 10 -6 and 10 -5 M concentrations (CSA: 12.6 ± 5.0 and 13.7 ± 8.8%, APV: 53.5 ± 21.9% and 37.8 ± 12.2% at 10 -6 and 10 -5 M respectively (p &lt; 0.01 in all cases)). Pre-treatment with ω Nitro-L-arginine methylester (L-NAME, 100 μM intracoronary) to block NO synthesis decreased testosterone-induced increase in CSA (13.4 vs. 8.0%, p = 0.06) and APV (89.4% vs. 39.8%, p = 0.06). Pre-treatment with gliben-clamide (10 -5 M) to assess role of ATP-sensitive K + channels did not attenuate testosterone-induced dilation in epicardial arteries though it did in the microcirculation (74.8vs. 32.8%, p = 0.03). Pre-treatment with indomethacin (5 mg/kg IV) did not alter changes. We conclude that acute testosterone-induced conductance coronary vasorelaxation is mediated in part by endothelium-derived NO. In contrast, ATP-sensitive K + channels appear to modulate testosterone effects on resistance arteries. The prostanoid system is not involved in either conductance or resistance coronary vascular relaxation.

Embryonic ventricular diastolic and systolic pressure-volume relations

SummaryThe embryonic heart and vascular bed interact dynamically to support rapid growth of the embryo during cardiovascular development. Pressure-volume relations define ventricular function during alterations in loading conditions. We analyzed these relationships in the embryonic heart in order to define ventricular function and the response of the ventricle and vascular bed to acute changes in preload. We simultaneously measured ventricular pressure and recorded 60 video images per second in n≥6 stage 16, 18 and 21 white Leghorn chick embryos at baseline and during the infusion of 1–2 microliters of physiologic buffer into the venous sinus (sinus venosus). Ventricular tetany was then induced with the topical application of 2 Molar sodium chloride. Video fields were traced for ventricular pressure and epicardial cross-sectional area. Cross-sectional area was converted to volume assuming ellipsoid geometry, and cavity volume was calculated as total volume minus wall volume derived from the tetanized heart. We defined end-diastole at the onset of ventricular contraction and end-systole at maximum pressure/volume ratio. Stroke volume increased linearly with end-diastolic volume. End-diastolic pressure-volume relations were positive and linear, and end-systolic pressure-volume relations were curvilinear downward. Arterial elastance decreased with growth of the embryo and with volume infusion. Pressure-volume loop area, an index of consumption of energy, doubled between the embryonic stages. Thus, embryonic ventricular pressure-volume relations define diastolic and systolic function at rest and in response to altered preload.

Effects of altered coronary perfusion pressure on function and metabolism of normal and cardiomyopathic hamster hearts

The effects of a sudden decrease in coronary perfusion pressure from 140 to 0 cmH2O for a 10-second interval were analyzed in normal and cardiomyopathic hamster hearts to determine whether cardiomyopathy would affect the relationship between altered coronary perfusion pressure and left ventricular geometry, wall thickness, myocardial hydrodynamics, and hemodynamics. In normal hamsters, an acute reduction in coronary perfusion pressure resulted in a decrease in left ventricular short axis epicardial cross-sectional area, base to apex length, diastolic wall thickness, myocardial water content and developed pressure. In cardiomyopathic hamsters all results induced by lowering the hydrostatic pressure of the perfusing medium were the same except that diastolic wall thickness failed to decline, indicating a decrease in intramyocardial elasticity in dilated cardiomyopathy. In parallel studies, hearts were freeze clamped at end-diastole and high energy phosphates and energy metabolites analyzed. In both normal and cardiomyopathic hamsters no significant changes were observed in ATP, PCr, or Pi levels at 10 s following the decrease in perfusion pressure. However, during the abrupt decrease in coronary perfusion pressure adenosine increased and cAMP decreased in both groups of animals. The erectile effect of altered coronary perfusion pressure is partially attenuated in the cardiomyopathic hamster in which no change in diastolic wall thickness occurs during an abrupt change in the hydrodynamics of the heart.