Reactive Hyperemic Response Research Articles

Effects of acute atrial fibrillation on the vasodilator reserve of the canine atrium.

Acute atrial fibrillation appreciably alters atrial physiology by increasing atrial blood flow and atrial oxygen consumption. To determine the effects of atrial fibrillation on atrial vasodilator reserve atrial fibrillation was produced in dogs by electrical atrial stimulation. Reactive hyperaemic responses were measured using Doppler crystals fixed to the sinus node artery and to an adjacent right ventricular branch artery during sinus rhythm, after 20 minutes of atrial fibrillation, and after systemic administration of chromonar (a potent coronary dilator) during atrial fibrillation. During sinus rhythm the peak to resting blood flow velocity ratio after a 20 s occlusion of the sinus node artery was 3.2(1) (mean(SEM)). A 20 s occlusion of a right ventricular branch artery during sinus rhythm resulted in a significantly larger response (5.9(0.7). The repayment to debt area ratio in response to a 20 s occlusion was 1.1(0.2) for the sinus node artery but 3.9(1.0) for a right ventricular branch. During atrial fibrillation the peak to resting velocity ratio was substantially decreased in the sinus node artery (2.3(0.6)) but was not significantly changed in the right ventricular branch (4.4(0.6)). Atrial fibrillation plus chromonar abolished reactive hyperaemia in both the sinus node artery and the right ventricular branch vessel. Right atrial blood flow (microspheres) increased from 45(4) in sinus rhythm to 106(19) ml X min-1 X 100 g-1 in atrial fibrillation and to 208(22) ml X min-1 X 100 g-1 after chromonar administration during atrial fibrillation. Thus the quantitative characteristics of coronary reactive hyperaemia in the right atrium were substantially different from those in the right ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of previous myocardial infarction on measurements of reactive hyperemia and the coronary vascular reserve

The measurement of coronary vascular reserve by the reactive hyperemic response to ischemia has been advocated as a practical method of assessing the physiologic significance of coronary stenoses. Because the concept of measuring coronary blood flow during maximal vasodilation assumes a normal arteriolar network and viable myocardium, the presence of previous myocardial infarction may cause a significant decrease in the coronary reserve unrelated to the severity of a coronary stenosis itself. To determine the potential importance of this effect, rest and hyperemic coronary blood flow were measured in 14 dogs in the regions subtended by the left anterior descending and left circumflex coronary arteries. One hour occlusion of the left anterior descending artery followed by reperfusion was performed in 10 dogs; the 4 remaining dogs in which no occlusion was performed served as control animals (group 3). One week later, rest and hyperemic blood flow measurements were repeated in all 14 dogs. Of the 10 dogs undergoing left anterior descending artery occlusion, 5 had a large infarct (group 1) and 5 had a small infarct (group 2). In group 1 in the 1 week study, both the coronary reserve in the left anterior descending artery zone and the ratio of the coronary reserve in this zone and the left circumflex artery zone decreased compared with values before occlusion (from 425 +/- 134 to 150 +/- 34% and from 1.56 +/- 0.40 to 0.68 +/- 0.31, respectively; both p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of diltiazem on myocardial recovery after regional ischemia in dogs

The effect of diltiazem on post-ischemic metabolic and functional recovery was investigated in regionally ischemic dog hearts. The duration of ischemia was 60 min, followed by 60 min of reperfusion. Diltiazem (bolus injection of 0.1 mg·kg −1 body weight prior to ischemia, followed by a continuous infusion of 0.1 mg·kg −1·h −1) had no effect on residual coronary flow in the centre of the ischemic area, but blunted the reactive hyperemia response after restoration of flow. The drug partially prevented the depletion of ATP and glycogen in the severely underperfused subendocardial layers, i.e. when residual flow was below 0.1 ml·min −1·g −1. Reduction of the content of these substances in the subepicardial layers was moderate and not influenced by diltiazem. Segment shortening in the subepicardial layers disappeared whereas segment lengthening was observed in the subendocardial layers during the ischemic period. Diltiazem did not prevent the loss of contractile function. Despite an initial restoration of contractile function within 10 min after reperfusion, no significant beneficial effect of diltiazem treatment on mechanical function of the reperfused area was present thereafter.

Periodic cutaneous blood flow during postocclusive reactive hyperemia.

Forearm cutaneous blood flow was monitored continuously by laser Doppler velocimetry in 10 normal human subjects before, during, and after external brachial artery occlusion for 6 min duration. During the reactive hyperemic response, the cutaneous blood flow exhibited rhythmic oscillatory activity. The amplitude of the oscillations was maximum 30 s postocclusion. Thereafter, the amplitude of the oscillations declined until cutaneous blood flow returned to control values. The mean (+/- SEM) period for the oscillations was 9.26 +/- 0.30 s. Bilateral forearm sites were examined simultaneously in eight studies and demonstrated a progressive loss of synchronicity. Nine additional studies were performed in which two forearm sites only 1.8 cm apart demonstrated a progressive loss of synchronicity resulting from different periodicities of microcirculatory flow patterns. These oscillations in cutaneous blood flow, which occur during postocclusive reactive hyperemia as a normal physiological phenomenon, are not synchronous in adjacent areas of skin. The data suggest an origin of the oscillations in the cutaneous vasculature that is either unrelated to sympathetic vasoconstrictor influences or is due to nonuniform cutaneous sympathetic excitation.

Effects of hypertension and hypercholesterolemia on vasodilatation in the rabbit.

Vasodilator substances act either directly on vascular smooth muscle (e.g., adenosine) or indirectly (e.g., acetylcholine) on endothelial cells that respond by releasing an unknown powerful, short-lived relaxing factor. To determine whether chronic hypertension or hypercholesterolemia or both would alter the release of the endothelium-derived relaxing factor, experiments were performed in hypertensive rabbits (5-week cellophane wrap perinephritis; mean blood pressure, 134.7 mm Hg) and normotensive rabbits (mean blood pressure, 80 mm Hg) with a Doppler flow transducer and perivascular balloon implanted on the lower abdominal aorta. Rabbits were fed either 1% cholesterol or control diet for 4 weeks before the experiment. On the day of the experiment, resting hindlimb vascular resistance was greatest in hypertensive rabbits fed 1% cholesterol diet, followed (in descending order) by hypertensive rabbits, normotensive rabbits fed 1% cholesterol diet, and normotensive rabbits. Pharmacological autonomic reflex blockade was induced, and steady state intravenous infusion curves to acetylcholine, serotonin, and adenosine were constructed. Sensitivity (location of effective dose, 50%) to the three vasodilator agents was altered less than twofold from the values in normotensive rabbits for any treatment group. The maximum vasodilator response to acetylcholine, but not to adenosine or serotonin, infusion was reduced significantly in the treated rabbits compared with that in normal rabbits. Reactive hyperemic responses to 5 to 80 seconds of ischemia were not significantly different among the treatment groups. These results indicate that hypertension with or without hypercholesterolemia does not greatly alter the responsiveness of the hindlimb resistance vasculature to these three vasodilator agents or to ischemia.

Reactive hyperemia following one-beat coronary occlusions in the awake dog.

This study was performed to examine the effect of alterations of cardiac activity during brief coronary artery occlusions on the subsequent reactive hyperemic response. Reactive hyperemia following coronary occlusions equal in duration to one cardiac cycle were examined in 12 chronically instrumented awake dogs while heart rate was maintained constant by cardiac pacing. During continuous pacing, one-beat coronary occlusions resulted in reactive hyperemia with excess flow equal to 220 +/- 23% blood flow debt repayment. When coronary occlusions of identical duration were performed while a single cycle of pacing was omitted during the interval of occlusion, the subsequent reactive hyperemia was decreased. Conversely, when coronary occlusion was produced during the first potentiated beat following a single cycle of paired ventricular stimulation, the reactive hyperemia was increased. Since, in the absence of coronary occlusion, omitting a single paced beat caused a transient decrease in coronary flow, while a single cycle of paired ventricular stimulation caused a brief increase in coronary flow, the reactive hyperemic responses were corrected for these perturbations in flow. Despite these corrections, the influence of alterations of myocardial activity during the interval of occlusion persisted, with the decreased reactive hyperemia when occlusion occurred during an omitted beat and increased hyperemia when occlusion was performed during a potentiated beat. These data indicate substantial coupling between myocardial activity during coronary occlusions as brief as one cardiac cycle in duration and the subsequent reactive hyperemic response.

Microcirculatory methods for the clinical assessment of hypertension, hypotension, and ischemia.

New techniques are now available for studying skin microcirculation non-invasively in humans. The clinically most useful ones are laser Doppler flowmetry, vital capillaroscopy, dynamic capillaroscopy and fluorescence microscopy. Some of these techniques have now been used in clinical practise for studying the reactivity of the skin microcirculation in patients with hypertension, hypotension and ischemia. It was found that the reactivity to stress in patients with hypertension can be quite different in the skin microvascular bed as compared to the total circulation of the region. In patients with local hypotension due to an arterial obstruction the postocclusive reactive hyperemia response is significantly changed compared to normals. The vasomotion activity is also decreased in the low pressure area. A marked decrease in the local blood pressure may lead to tissue ischemia. In these patients the risk of skin necrosis can be evaluated by microscopic classification of the structural changes of the capillaries in the area of ischemia. When the skin capillaries are void of erythrocytes the risk of necrosis is imminent.

Effects of perfusion pressure and adenosine infusion on the reactive hyperaemic response of the coronary circulation

Effects of perfusion pressure and adenosine infusion on the reactive hyperaemic response of the coronary circulation

Thyroxine-induced left ventricular hypertrophy in the rat. Anatomical and physiological evidence for angiogenesis.

We examined anatomical and physiological responses of the left coronary vascular system to thyroxine-induced myocardial hypertrophy. Wistar-Kyoto rats (1 and 5 months old) were administered thyroxine (0.25 mg/kg per day) or the saline vehicle (sham-treated controls) for 2 months. At the ages of 3 and 7 months, each group of animals was used for one of three experimental protocols: determination of numerical capillary density in perfusion-fixed hearts, measurement of coronary reactive hyperemic responses following a 20-second coronary occlusion (peak-to-resting blood flow velocity) as an index of coronary reserve, and assessment of myocardial perfusion under resting conditions and during maximum coronary dilation (dipyridamole infusion) for the calculation of minimum coronary resistance per unit weight of the left ventricle or minimum coronary resistance of the total left ventricle. In both groups of thyroxine-treated animals, the left ventricular weight-to-body weight ratio increased by 35-40%. Capillary density of the 3- and 7-month-old Wistar Kyoto controls was 4467 +/- 352 (mean +/- SEM) and 4029 +/- 143 capillaries/mm2, respectively, but was increased significantly in the thyroxine-treated animals to 6052 +/- 409 capillaries/mm2 (3-month) and 4654 +/- 201 capillaries/mm2 (7-month). In both age control groups, the peak-to-resting blood flow velocity ratio was about 2.2. This index of coronary reserve was not changed in the thyroxine-treated animals. Myocardial perfusion measurements were limited to the 7-month-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of coronary resistance vessels and large coronary arteries

There is now considerable evidence for α-adrenergic regulation of coronary resistance vessels and large coronary arteries based on studies of chronically instrumented, conscious animals. Infusion of norepinephrine at low doses causes reduction of coronary blood flow with a slight increase in arterial pressure, indicating intense coronary vasoconstriction. This coronary constrictor response was reversed to coronary vasodilation with infusion of norepinephrine after α-adrenergic blockade. Stimulation of α 1- and α 2-adrenergic receptors with phenylephrine and B-HT 920, respectively, also increased calculated coronary vascular resistance in the conscious animal. These effects were eliminated by selective α 1-adrenergic blockade with prazosin and by selective α 2-adrenergic blockade with rauwolscine. Stimulation of the carotid chemoreceptor reflex elicits a period of intense coronary vasoconstriction, characterized by a decrease in coronary blood flow despite increased arterial driving pressure. This response was eliminated by prior α-adrenergic blockade or a combination of cardiac sympathetic denervation and adrenalectomy. Using chronically implanted ultrasonic crystals to measure the epicardial coronary diameter instantaneously and continuously in conscious dogs, marked vasodilation of the large coronary arteries was observed with administration of nitroglycerin or calcium-channel antagonists; in contrast, activation of α-adrenergic receptors with methoxamine induced substantial constriction, characterized by a reduction in coronary artery diameter in the face of elevated distending pressure. The regulation of large coronary arteries is further complicated by the fact that these vessels are responsive to changes in myocardial metabolic demands and coronary blood flow. This was demonstrated by examining responses to brief periods of myocardial ischemia, which induced intense reactive dilation, i.e., dilation of the large coronary artery immediately after the reactive hyperemia response. The dilation of the large coronary artery was not observed after brief periods of myocardial ischemia, when the marked increase in coronary blood flow (reactive hyperemia) was prevented. These findings suggest that coronary artery vasconstriction may be more intense under conditions in which blood flow cannot increase, for example, in the presence of severe stenoses.

Effect of adenosine deaminase inhibitors on myocardial reactive hyperaemia following brief coronary occlusions

Effect of two agents of adenosine deaminase inhibitor, 8-azaguanine and adenine, on myocardial reactive hyperaemia was tested in the anaesthetised open-chest dog. Reactive hyperaemic flow response of the circumflex coronary artery was observed following 5, 10, 15, 20 and 30 s coronary occlusions before, during and after infusion of 8-azaguanine and adenine, which are known as adenosine deaminase inhibitors. Intracoronary infusion of 8-azaguanine and adenine caused the minimum increase in the baseline coronary flow. Both the nucleic acids shifted the dose response curve of adenosine to the left. 8-azaguanine enhanced volume response of flow at all occlusion intervals tested. The infused dose of adenine also intensified volume response of flow after 5, 15, 20 and 30 s occlusions. Fifteen minutes after termination of the nucleic acid infusions, the reactive hyperaemia returned towards control levels. The results suggest that 8-azaguanine and adenine enhance myocardial reactive hyperaemia possibly by inhibiting adenosine deaminase to degradate myocardial interstitial adenosine to inosine.

Cutaneous postocclusive reactive hyperemia monitored by Laser Doppler Flux metering and skin temperature

The initial Laser Doppler Flux (LDF) values and skin temperature in the first, third, and fifth finger were evaluated as well as the postocclusion reactive hyperemia (PORH) response to a 4-min suprasystolic compression. The mean values varied from 276.5 to 335.3 mV while the skin temperature ranged from 32.5 to 34.2°. The LDF-monitored PORH response was very reproducible with an average increase of 144.7 ± 63.6 mV (from an initial LDF value of 327.1 ± 134 mV). Four different time-related indices were analyzed: t 2 recovery = 6.0 ± 5.5 sec; t recovery ( time to reach the initial value) = 16.7 ± 11.5 sec; t max ( peak of overshoot) = 48.2 ± 20.6 sec and t 2 overshoot (time to reach 50% of the t max on the downslope) = 97.4 ± 31.8 sec . The simultaneously monitored skin temperature changes lagged significantly behind the LDF changes probably due to the large heat capacitance of the tissue. It is expected that the described results obtained from 20 normal subjects will serve as a basis for future clinical studies involving skin perfusion disorders.

Transluminal, subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man.

Assessment of coronary blood flow and the vasodilator reserve capacity of individual coronary arteries in the catheterization laboratory has been hampered by methodologic limitations. We have developed and validated a small Doppler catheter that can subselectively measure phasic coronary blood flow velocity (CBFV). In seven anesthetized calves, CBFV was varied from 0.1 to 5.7 times control CBFV. Changes in mean CBFV measured intraluminally by catheter in the left anterior descending and left circumflex arteries were similar to those measured simultaneously with an epicardial Doppler probe on the surface of the same vessel (n = 85, r = .95, slope = 1.04) and to changes in coronary sinus flow (n = 69, r = .97, slope = 1.06) measured with timed venous collections. Identical maximal coronary reactive hyperemic responses with the catheter present and absent in the artery being studied demonstrated that coronary obstruction by the catheter was minimal. Safety studies in six additional calves demonstrated that the catheter caused small changes in coronary endothelial permeability. Histologic studies revealed no endothelial denudation or thrombus formation. Stable phasic recordings of coronary blood flow velocity have been obtained in 58 of 70 patients studied. One of the 70 patients studied had abrupt coronary occlusion probably related to catheter-induced vasospasm. In 10 normal patients, intracoronary meglumine diatrizoate increased CBFV to 3.5 times that at rest (range 2.8 to 5.0). CBFV rose 5.0-fold after an intravenous infusion of dipyridamole (range 3.8 to 7.0). In each patient, dipyridamole produced greater vasodilation than meglumine diatrizoate. The time- and dose-response characteristics to dipyridamole infusion were heterogeneous, underscoring the advantage of continuous on-line measurement of CBFV in the measurement of vasodilator reserve. This method of measuring CBFV and assessing vasodilator reserve in the catheterization laboratory should facilitate studies of the coronary circulation in man.

Functional and reactive hyperemia are unaltered by homocysteine in conscious dogs

The purpose of this study was to test the hypothesis that L-homocysteine thiolactone (L-HCTL), through its reaction with adenosine to form S-adenosylhomocysteine, may modulate myocardial functional and reactive hyperemic responses. Reactive hyperemic responses to 10-sec occlusions or 400-msec diastolic occlusions of the circumflex coronary artery and functional hyperemic responses to ventricular extra-activations were studied in a chronic heart-blocked dog preparation during a control period and following L-HCTL (40 mg/kg). In two additional dogs multiple venous blood samples and left ventricular myocardial biopsies were obtained following L-HCTL to measure changes in plasma homocysteine and tissue S-adenosylhomocysteine. Despite a 75-fold increase in peak plasma homocysteine and a 26-fold increase in tissue S-adenosylhomocysteine, L-HCTL did not alter myocardial functional and reactive hyperemic responses. The rapid increase in myocardial S-adenosylhomocysteine confirmed cellular entry of homocysteine and its reaction with endogenous adenosine. The failure of L-HCTL to alter functional and reactive hyperemic responses suggests that either such treatment does not affect myocardial release of adenosine or that adenosine is not an important regulator of coronary flow.

Dynamics of Skin Microcirculation in Humans

The human cutaneous microcirculation has so far been studied by rather crude methods, such as plethysmography and 133Xn clearance. New sophisticated and noninvasive techniques are now available, with which the microcirculation of the skin can be continuously studied and measured for hours. With two such methods, i.e., Laser-Doppler flowmetry and dynamic capillaroscopy, fast dynamic fluctuations of the microcirculation can be followed. Under resting conditions, the total skin flow of a small area (1-2 mm2) varies consistently with time. These variations are caused by the arterial pulse, but also by active vasomotion with a frequency of about 4-8 cycles/min. These fluctuations can also be seen in single skin capillaries, but with a somewhat faster frequency: 6-10 cycles/min. The reaction of the cutaneous microcirculation to provocation tests, such as postocclusive reactive hyperemia response and venous occlusion (50 mm Hg), can also be studied. The time to peak during postocclusive reactive hyperemia is very consistent. In response to venous congestion, capillary flow rate falls drastically, whereas Laser-Doppler flow is much less dramatically reduced. These discrepancies suggest that the Laser-Doppler flowmeter records blood flow in skin vessels in addition to the superficial, nutritional capillaries. The dynamic pattern of the skin microcirculation is altered in patients with hypertension, diabetes, and obstructive arterial disease.

Effects of long-term cardiac hypertrophy on coronary vasodilator reserve in SHR rats

The effects of long-term left ventricular (LV) hypertrophy on coronary vascular reserve have not been extensively investigated. To test the hypothesis that the duration of LV hypertrophy may modulate coronary vascular reserve, a newly developed pulsed Doppler flowmeter was used to compare the characteristics of coronary reactive hyperemia in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The data suggest that coronary reactive hyperemic responses in the rat are markedly different from those in larger animals and humans, e.g., peak/rest blood flow velocity ratio and the repayment/debt area ratio were 30 to 50% of those observed in larger laboratory animals. Because minimal coronary vascular resistance is similar in the rat and larger animals, the relatively high myocardial oxygen consumption at rest and consequent high myocardial blood flow at rest probably account for the alteration of coronary reactive hyperemia in the rat. In SHR rats, the characteristics of coronary reactive hyperemia decreased during developing (3-month-old) and peak (7-month-old) LV hypertrophy compared with those in their age-matched WKY controls. However, in 12-month-old SHR rats with stable LV hypertrophy, the coronary reactive hyperemic response was similar to that of 12-month-old WKY rats. Mean arterial pressures were significantly elevated in each of the 3 SHR groups. These data suggest a significant decrement in coronary vascular reserve during actively developing and peak LV hypertrophy, but the decrement disappears during stabilized hypertrophy. These studies suggest that the duration of LV hypertrophy may modulate the interaction between pathologic increases in cardiac mass and growth of the coronary vasculature.

Development of collateral function with repetitive coronary occlusion in a canine model reduces myocardial reactive hyperemia in the absence of significant coronary stenosis.

The present study was designed to elucidate the role of collateral development, per se, on reactive hyperemia without persistent coronary stenosis in instrumented conscious dogs. Functional states of coronary collaterals were augmented by repetitive 2 minutes of coronary occlusion every 30 minutes for 2-9 days. Regional shortening measured sonomicrometrically recovered from -1.2 +/- 6.5% of the preocclusive state at the end of the first coronary occlusion to 100.5 +/- 1.2% (n = 8, P less than 0.01) after repeated coronary occlusions. Before and after collateral development, transient coronary occlusions of 5, 10, 20, 30, 60, 90, and 120 seconds were randomly performed. The degree of regional dysfunction and the following reactive hyperemic response were measured. Up to 20 seconds of coronary occlusion, the flow ratio and duration of coronary reactive hyperemia increased similarly, both before and after collateral development. However, when the duration of coronary occlusion was over 30 seconds, flow ratio and debt repayment ratio were reduced progressively after the collateral development. Among the indices exhibiting reactive hyperemia, debt repayment ratio decreased initially and correlated well with the recovery of regional dysfunction during coronary occlusion. Thus, the augmentation of collateral function after repetitive coronary occlusion reduces reactive hyperemia even in the absence of significant coronary stenosis.

β-Blocking and Hemodynamic Effects of ASL-8052

The hemodynamic and cardiac beta-blocking effects of ASL-8052 (esmolol), an ultrashort-acting beta-blocker, were examined in pentobarbital-anesthetized dogs. The compound produced dose-dependent reductions in heart rate, left ventricular dP/dt, right ventricular contractile force, and diastolic arterial blood pressure in dogs with intact autonomic function. ASL-8052 was devoid of any hemodynamic effects in ganglion-blocked animals. Responses to isoproterenol (except for diastolic blood pressure) were blocked by ASL-8052 in qualitatively similar fashion in both groups of animals. The compound reduced the rate-pressure product and decreased diastolic coronary blood flow. The reactive hyperemic response to a 10-s occlusion of the left circumflex coronary artery was not modified by ASL-8052. Heart rate and contractile force dose-response curves to isoproterenol were equally shifted to the right in a dose-dependent, parallel fashion by constant infusion of ASL-8052. During infusion of large doses in reserpinized dogs, the compound decreased heart rate, contractility, and arterial blood pressure, while left ventricular end-diastolic pressure increased. No intrinsic sympathomimetic effect was observed. Tachycardia induced by either stimulation of the right ansa subclavia or intravenous injection of isoproterenol was blocked to an equivalent degree by ASL-8052. These data indicate that ASL-8052 produces hemodynamic effects that are characteristic of and explained by beta-adrenergic receptor blockade. However, direct cardiac depression is observed at extremely high doses.

Coronary Vasodilator Reserve in Young Dogs with Moderate Right Ventricular Hypertrophy

The effects of experimental right ventricular (RV) pressure overload and RV hypertrophy on coronary vasodilator reserve in young animals is not well established. Therefore, we measured coronary vasodilator reserve in the right ventricle of dogs from 7 to 12 months old with moderate RV hypertrophy due to pulmonary artery banding performed 3 to 7 days after birth. In the 5 dogs with pulmonary artery banding, substantial RV hypertension developed (RV pressure at rest, 73 ± 11 mm Hg) as did RV hypertrophy (ratio of RV free wall/left ventricular free wall weight, 1.86 ± 0.41 gm/kg). The reactive hyperemic response following brief coronary occlusions was used as an index of coronary vasodilator reserve. The ratios of peak reactive hyperemic response to resting flow, however, were not significantly different in the 5 banded dogs compared with 7 control animals (3.6 ± 1.0 versus 2.6 ± 0.6); this implies that the extent of vasodilator reserve was similar with or without moderate RV hypertrophy. In addition, myocardial blood flow, as determined using radioactive microspheres, was not significantly different at rest: 0.57 ± 0.09 ml/min per gram in the banded dogs versus 0.48 ± 0.12 ml/min per gram in the controls. Uniform transmural distribution of blood flow was maintained during infusion of isoproterenol, which was used to increase myocardial oxygen requirements in both groups. Minimum coronary vascular resistance was significantly lower in the banded than the control dogs (1.5 ± 0.6 versus 6.2 ± 2.3; p < 0.01). This difference suggests that the cross-sectional area of the right coronary vascular bed increased with the development of RV hypertrophy.

Effect of aminophylline on coronary reactive and functional hyperaemic response in conscious dogs.

This study was undertaken to determine whether adenosine release from myocardial cells plays a role in coronary reactive and functional vasomotion. Reactive hyperaemic blood flow responses to 10 s complete occlusions and 400 ms diastolic occlusions of the left circumflex coronary artery and to the vasomotor responses to the increased cardiac demand following ventricular extra-activation were examined in a chronic, heart-blocked dog preparation during a control period and following intravenous bolus administration of aminophylline (5 mg X kg-1). Aminophylline administration resulted in a 19% decrease in the blood flow debt repayment ratio of 10 s reactive hyperaemic responses compared with the control period. However, administration of aminophylline had no effect on the coronary vascular response to 400 ms diastolic occlusions or to ventricular extra-activations. These observations indicate that adenosine may play a role in the coronary vascular response to prolonged interventions but that other factors, as yet unidentified, may be implicated in the beat-to-beat regulation of coronary vascular resistance.