Plasma ATP during exercise: possible role in regulation of coronary blood flow

It was previously shown that red blood cells release ATP when blood oxygen tension decreases. ATP acts on microvascular endothelial cells to produce a retrograde conducted vasodilation (presumably via gap junctions) to the upstream arteriole. These observations form the basis for an ATP hypothesis of local metabolic control of coronary blood flow due to vasodilation in microvascular units where myocardial oxygen extraction is high. Dogs (n = 10) were instrumented with catheters in the aorta and coronary sinus, and a flow transducer was placed around the circumflex coronary artery. Arterial and coronary venous plasma ATP concentrations were measured at rest and during three levels of treadmill exercise by using a luciferin-luciferase assay. During exercise, myocardial oxygen consumption increased approximately 3.2-fold, coronary blood flow increased approximately 2.7-fold, and coronary venous oxygen tension decreased from 19 to 12.9 mmHg. Coronary venous plasma ATP concentration increased significantly from 31.1 to 51.2 nM (P < 0.01) during exercise. Coronary blood flow increased linearly with coronary venous ATP concentration (P < 0.01). Coronary venous-arterial plasma ATP concentration difference increased significantly during exercise (P < 0.05). The data support the hypothesis that ATP is one of the factors controlling coronary blood flow during exercise.     

Feedforward sympathetic coronary vasodilation in exercising dogs.

The hypothesis that exercise-induced coronary vasodilation is a result of sympathetic activation of coronary smooth muscle beta-adrenoceptors was tested. Ten dogs were chronically instrumented with a flow transducer on the circumflex coronary artery and catheters in the aorta and coronary sinus. During treadmill exercise, coronary venous oxygen tension decreased with increasing myocardial oxygen consumption, indicating an imperfect match between myocardial blood flow and oxygen consumption. This match was improved after alpha-adrenoceptor blockade with phentolamine but was significantly worse than control after alpha + beta-adrenoceptor blockade with phentolamine plus propranolol. The response after alpha-adrenoceptor blockade included local metabolic vasodilation plus a beta-adrenoceptor vasodilator component, whereas the response after alpha + beta-adrenoceptor blockade contained only the local metabolic vasodilator component. The large difference in coronary venous oxygen tensions during exercise between alpha-adrenoceptor blockade and alpha + beta-adrenoceptor blockade indicates that there is significant feedforward beta-adrenoceptor coronary vasodilation in exercising dogs. Coronary venous and estimated myocardial interstitial adenosine concentrations did not increase during exercise before or after alpha + beta-adrenoceptor blockade, indicating that adenosine levels did not increase to compensate for the loss of feedforward beta-adrenoceptor-mediated coronary vasodilation. These results indicate a meaningful role for feedforward beta-receptor-mediated sympathetic coronary vasodilation during exercise.     

Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise

The purpose of this investigation was to quantitatively evaluate the role of adenosine in coronary exercise hyperemia. Dogs (n = 10) were chronically instrumented with catheters in the aorta and coronary sinus, and a flow probe on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous plasma concentrations using a previously tested mathematical model. Coronary blood flow, myocardial oxygen consumption, heart rate, and aortic pressure were measured at rest and during graded treadmill exercise with and without adenosine receptor blockade with either 8-phenyltheophylline (8-PT) or 8-p-sulfophenyltheophylline (8-PST). In control vehicle dogs, exercise increased myocardial oxygen consumption 4.2-fold, coronary blood flow 3.8-fold, and heart rate 2.5-fold, whereas mean aortic pressure was unchanged. Coronary venous plasma adenosine concentration was little changed with exercise, and the estimated interstitial adenosine concentration remained well below the threshold for coronary vasodilation. Adenosine receptor blockade did not significantly alter myocardial oxygen consumption or coronary blood flow at rest or during exercise. Coronary venous and estimated interstitial adenosine concentration did not increase to overcome the receptor blockade with either 8-PT or 8-PST as would be predicted if adenosine were part of a high-gain, negative-feedback, local metabolic control mechanism. These results demonstrate that adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise.     

Quantitative analysis of feedforward sympathetic coronary vasodilation in exercising dogs.

Recent experiments demonstrate that feedforward sympathetic beta-adrenoceptor coronary vasodilation occurs during exercise. The present study quantitatively examined the contributions of epinephrine and norepinephrine to exercise coronary hyperemia and tested the hypothesis that circulating epinephrine causes feedforward beta-receptor-mediated coronary dilation. Dogs (n = 10) were chronically instrumented with a circumflex coronary artery flow transducer and catheters in the aorta and coronary sinus. During strenuous treadmill exercise, myocardial oxygen consumption increased by approximately 3.9-fold, coronary blood flow increased by approximately 3.6-fold, and arterial plasma epinephrine concentration increased by approximately 2.4-fold over resting levels. At arterial concentrations matching those during strenuous exercise, epinephrine infused at rest (n = 6) produced modest increases (18%) in flow and myocardial oxygen consumption but no evidence of direct beta-adrenoceptor-mediated coronary vasodilation. Arterial norepinephrine concentration increased by approximately 5. 4-fold during exercise, and coronary venous norepinephrine was always higher than arterial, indicating norepinephrine release from cardiac sympathetic nerves. With the use of a mathematical model of cardiac capillary norepinephrine transport, these norepinephrine concentrations predict an average interstitial norepinephrine concentration of approximately 12 nM during strenuous exercise. Published dose-response data indicate that this norepinephrine concentration increases isolated coronary arteriolar conductance by approximately 67%, which can account for approximately 25% of the increase in flow observed during exercise. It is concluded that a significant portion of coronary exercise hyperemia ( approximately 25%) can be accounted for by direct feedforward beta-adrenoceptor coronary vascular effects of norepinephrine, with little effect from circulating epinephrine.     

Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction

The renin-angiotensin system plays an important role in cardiovascular homeostasis by contributing to the regulation of blood volume, blood pressure, and vascular tone. Because AT(1) receptors have been described in the coronary microcirculation, we investigated whether ANG II contributes to the regulation of coronary vascular tone and whether its contribution is altered during exercise. Since the renin-angiotensin system is activated after myocardial infarction, resulting in an increase in circulating ANG II, we also investigated whether the contribution of ANG II to the regulation of vasomotor tone is altered after infarction. Twenty-six chronically instrumented swine were studied at rest and while running on a treadmill at 1-4 km/h. In 13 swine, myocardial infarction was induced by ligation of the left circumflex coronary artery. Blockade of AT(1) receptors (irbesartan, 1 mg/kg iv) had no effect on myocardial O(2) consumption but resulted in an increase in coronary venous O(2) tension and saturation both at rest and during exercise, reflecting coronary vasodilation. Despite increased plasma levels of ANG II after infarction and maintained coronary arteriolar AT(1) receptor levels, the vasodilation evoked by irbesartan was significantly reduced both at rest and during exercise. In conclusion, despite elevated plasma levels, the vasoconstrictor influence of ANG II on the coronary circulation in vivo is reduced after myocardial infarction. This reduction in ANG II-induced coronary vasoconstriction may serve to maintain perfusion of the remodeled myocardium.     

Ascending pathways mediating somatoautonomic reflexes in exercising dogs

The ascending spinal pathways mediating somatocardiovascular reflexes during exercise were studied in unanesthetized dogs by placing lesions in the lumbar spinal cord. After training to run on a treadmill with hindlimbs only, 20 dogs were anesthetized and instrumented using sterile surgical techniques. To chronically record heart rate and arterial blood pressure, the aorta was cannulated via the omocervical artery. To test the intactness of descending spinal sympathetic pathways, reflex pressor responses to baroreceptor hypotension were produced by bilateral carotid arterial occlusion using pneumatic vessel occluders placed around the common carotid arteries. To generate transient ischemic exercise (120 s), a pneumatic occluder was placed around the left iliac artery. Eight to 10 days after instrumentation, blood pressure and heart rate were monitored at rest and during hindlimb running with and without simultaneous iliac arterial occlusion. The modest pressor response and tachycardia elicited by hindlimb exercise were markedly augmented by simultaneous hindlimb ischemia (i.e., iliac arterial occlusion). Lesion placement in the dorsolateral sulcus area and the dorsolateral funiculus at L2 significantly reduced the blood pressure and heart rate responses to simultaneous exercise occlusion. The cardiovascular responses to nonischemic exercise and bilateral carotid arterial occlusion were not altered by such spinal sections. It is concluded that in the dog the ascending spinal pathways mediating cardiovascular responses to ischemic exercise are located in the lateral funiculus, including the dorsolateral sulcus area and dorsolateral funiculus.     

K(ATP)(+) channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation

The role of ATP-sensitive K(+) (K(ATP)(+)) channels, nitric oxide, and adenosine in coronary exercise hyperemia was investigated. Dogs (n = 10) were chronically instrumented with catheters in the aorta and coronary sinus and instrumented with a flow transducer on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous plasma concentrations using a previously tested mathematical model. Experiments were conducted at rest and during graded treadmill exercise with and without combined inhibition of K(ATP)(+) channels (glibenclamide, 1 mg/kg iv), nitric oxide synthesis (N(omega)-nitro-L-arginine, 35 mg/kg iv), and adenosine receptors (8-phenyltheophylline, 3 mg/kg iv). During control exercise, myocardial oxygen consumption increased ~2.9-fold, coronary blood flow increased ~2.6-fold, and coronary venous oxygen tension decreased from 19.9 +/- 0.4 to 13.7 +/- 0.6 mmHg. Triple blockade did not significantly change the myocardial oxygen consumption or coronary blood flow response during exercise but lowered the resting coronary venous oxygen tension to 10.0 +/- 0.4 mmHg and during exercise to 6.2 +/- 0.5 mmHg. Cardiac adenosine levels did not increase sufficiently to overcome the adenosine receptor blockade. These results indicate that combined inhibition of K(ATP)(+) channels, nitric oxide synthesis, and adenosine receptors lowers the balance between total oxygen supply and consumption at rest but that these factors are not required for local metabolic coronary vasodilation during exercise.     

Distribution of blood flow during exercise after blood volume expansion in swine

To study the distribution of blood flow after blood volume expansion, seven miniature swine ran at high speed (17.6-20 km/h, estimated to require 115% of maximal O2 uptake) on a motor-driven treadmill on two occasions: once during normovolemia and once after an acute 15% blood volume expansion (homologous whole blood). O2 uptake, cardiac output, heart rate, mean arterial pressure, and distribution of blood flow (with radiolabeled microspheres) were measured at the same time during each of the exercise bouts. Maximal heart rate was identical between conditions (mean 266); mean arterial pressure was elevated during the hypovolemic exercise (149 +/- 5 vs. 137 +/- 6 mmHg). Although cardiac output was higher and arterial O2 saturation was maintained during the hypervolemic condition (10.5 +/- 0.7 vs. 9.3 +/- 0.6 l/min), O2 uptake was not different (1.74 +/- 0.08 vs. 1.74 +/- 0.09 l/min). Mean blood flows to cardiac (+12.9%), locomotory (+9.8%), and respiratory (+7.5%) muscles were all elevated during hypervolemic exercise, while visceral and brain blood flows were unchanged. Calculated resistances to flow in skeletal and cardiac muscle were not different between conditions. Under the experimental conditions of this study, O2 uptake in the miniature swine was limited at the level of the muscles during hypervolemic exercise. The results also indicate that neither intrinsic contractile properties of the heart nor coronary blood flow limits myocardial performance during normovolemic exercise, because both the pumping capacity of the heart and the coronary blood flow were elevated in the hypervolemic condition.     

Exercise training increases coronary transport reserve in miniature swine

Female yucatan miniature swine were trained on a treadmill (ET) or were cage confined (C) for 16-22 wk. The ET pigs had increased exercise tolerance, heart weight-to-body weight ratio, and skeletal muscle oxidative capacity. After anesthesia the left anterior descending coronary artery was cannulated and pump perfused with blood while aortic, central venous, and coronary perfusion pressures, electrocardiogram, heart rate, and coronary blood flow were monitored. Capillary permeability-surface area product (PS) for EDTA was determined with the single-injection indicator-diffusion method by use of an organ model based on the Sangren-Sheppard equations for capillary transport. Coronary blood flow (CBF) and PS were compared before and during maximal adenosine vasodilation with coronary perfusion pressures at 120 mmHg. Results indicate that there were no differences in base-line CBF or PS between C and ET groups. alpha-Receptor blockade with phentolamine and/or prazosin, before adenosine vasodilation, produced increases in PS in C pigs but had little effect in ET pigs. During maximal vasodilation with adenosine, ET pigs had greater CBF (447 +/- 24 vs. 366 +/- 27 ml.min-1.100 g-1) and greater PS (83 +/- 9 vs. 55 +/- 7 ml.min-1.100 g-1) than the C group. It is concluded that ET induces an increased coronary transport capacity in miniature swine that includes a 22% increase in blood flow capacity and a 51% increase in capillary exchange capacity.     

Respiratory, cardiovascular, and metabolic adjustments to exercise in the Hereford calf

Six Hereford steers were studied before, during, and after short exercise bouts on a motor-driven treadmill (3 degrees incline) at four speeds (1.0, 1.4, 1.8, and 2.2 m X s-1). Oxygen consumption (MO2) and carbon dioxide production (MCO2) were measured by collecting the expired gas. Arterial and mixed venous blood samples were obtained simultaneously from indwelling catheters in the aorta and pulmonary artery. A 10-fold increase was observed in MO2 and MCO2 at the highest work load. Minute ventilation increased proportionately less than MO2 and MCO2 with increasing work loads, but alveolar ventilation was found to increase in proportion to both MO2 and MCO2. The highest work load produced a threefold increase in cardiac output primarily as a result of increased heart rate. A 10-fold increase in lactate and a 63% increase in serum potassium concentration were observed at the highest work load. Plasma cortisol levels were highest at 10 min postexercise and reached levels of seven times the resting values following exercise at the highest speed. The responses to exercise in the calf are qualitatively similar to those observed in other species, but quantitative differences exist in some cardiovascular and metabolic responses which may limit this animal's ability to perform strenuous exercise.     

Renal blood flow distribution during steady-state exercise and exhaustion in conscious dogs.

To determine whether renal blood flow is reduced or redistributed during exercise, we measured total renal flow (TRF) and intrarenal flow distribution (IRFD) in nine dogs. They ran on a motor-driven treadmill at 3-8 mph at grades of 8-15% for an average of 35 min. We measured aortic pressure, heart rate, stroke volume, and cardiac output (CO) via chronically implanted catheters and an electromagnetic flow probe. We injected 15-mum radiolabeled microspheres (85Sr, 141Ce, and 51Cr) via a left atrial catheter during resting control, steady state (SS) and exhaustive (EE) exercise; measured their distribution by gamma spectrometry; and determined TRF as % CO and as ml/100 g per min. We determined IRFD for the outer and inner cortex and the outer medulla. TRF as %CO dropped (P less than 0.05) during both levels of exercise: from 10.2 +/- 0.7% to 3.9 +/- 0.4% (SS) and 3.4 +/- 0.6% (EE). TRF in ml/100 g per min did not change significantly from control (228 +/- 30 ml/100 g per min). IRFD was unchanged with exercise, remaining at about 80, 20, and 3% of TRF for the outer and inner cortex and outer medulla, respectively. We conclude that blood flow is not diverted from the kidneys during severe exercise in the dog.     

Acidaemia reduces cardiac output and left ventricular contractility in conscious lambs

We studied the effects of HCI-induced metabolic acidaemia on cardiac output, contractile function, myocardial blood flow, and myocardial oxygen consumption in nine unanaesthetized newborn lambs. Through a left thoracotomy, catheters were placed in the aorta, left atrium and coronary sinus. A pressure transducer was placed in the left ventricle. Three to four days after surgery, we measured cardiac output, dP/dt, left ventricular end diastolic and aortic mean blood pressures, heart rate, aortic and coronary sinus blood oxygen contents, and left ventricular myocardial blood flow during a control period, during metabolic acidaemia, and after the aortic pH was restored to normal. We calculated systemic vascular resistance, myocardial oxygen consumption and left ventricular work. Acidaemia was associated with reduction in cardiac output, maximal dP/dt, and aortic mean blood pressure. Left ventricular end diastolic pressure and systemic vascular resistance increased, and heart rate did not change significantly. The reduction in myocardial blood flow and oxygen consumption was accompanied by fall in cardiac work. Cardiac output returned to control levels after the pH had been normalized but maximal dP/dt was incompletely restored. Myocardial blood flow and oxygen consumption increased beyond control levels. This study demonstrates that HCI-induced metabolic acidaemia in conscious newborn lambs is associated with a reduction in cardiac output which could have been mediated by the reduction in contractile function and/or the increase in systemic vascular resistance. The decreases in myocardial blood flow and oxygen consumption appear to reflect diminished cardiac work. The restoration of a normal cardiac output after normalization of the pH appears to have resulted from the increases in heart rate and left ventricular filling pressures in conjunction with an incomplete restoration of contractile function.     

Alpha-adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in experimental diabetes mellitus.

This study tested whether alpha-adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in diabetes mellitus. Experiments were conducted in dogs instrumented with catheters in the aorta and coronary sinus and with a flow transducer around the circumflex coronary artery. Diabetes was induced with alloxan monohydrate (n = 8, 40 mg/kg i.v.). Arterial plasma glucose concentration increased from 4.7 +/- 0.2 mM in nondiabetic, control dogs (n = 8) to 21.4 +/- 1.9 mM 1 wk after alloxan injection. Coronary blood flow, myocardial oxygen consumption (MVo(2)), aortic pressure, and heart rate were measured at rest and during graded treadmill exercise before and after infusion of the alpha-adrenoceptor antagonist phentolamine (1 mg/kg iv). In untreated diabetic dogs, exercise increased MVo(2) 2.7-fold, coronary blood flow 2.2-fold, and heart rate 2.3-fold. Coronary venous Po(2) fell as MVo(2) increased during exercise. After alpha-adrenoceptor blockade, exercise increased MVo(2) 3.1-fold, coronary blood flow 2.7-fold, and heart rate 2.1-fold. Relative to untreated diabetic dogs, alpha-adrenoceptor blockade significantly decreased the slope of the relationship between coronary venous Po(2) and MVo(2). The difference between the untreated and phentolamine-treated slopes was greater in the diabetic dogs than in the nondiabetic dogs. In addition, the decrease in coronary blood flow to intracoronary norepinephrine infusion was significantly augmented in anesthetized, open-chest, beta-adrenoceptor-blocked diabetic dogs compared with the nondiabetic dogs. These findings demonstrate that alpha-adrenoceptor-mediated coronary vasoconstriction is augmented in alloxan-induced diabetic dogs during physiological increases in MVo(2).     

Tracheobronchial perfusion during exercise in ponies

Tracheobronchial circulation during exercise has previously not been examined. Therefore blood flow to the trachea and bronchi (up to 7th generation of branching) was studied in seven healthy adult ponies at rest and during the 3rd and 10th min of exercise performed at a treadmill speed setting of 25 km/h. The ambient air temperature varied from 19 to 20 degrees C and humidity from 35 to 45%. To determine blood flow radionuclide-labeled 15-microns-diameter microspheres were injected into the left ventricle via a catheter advanced from the left carotid artery (exposed using local anesthesia), and a reference sample was obtained from the aorta. Adequate mixing of microspheres with blood was demonstrated by similar perfusion values for left and right kidneys. Exercise increased heart rate (194 +/- 9 and 200 +/- 7 beats/min) and mean aortic pressure (169 +/- 8 and 156 +/- 4 mmHg) of ponies at 3rd and 10th min. Tracheal blood flow (6.7 +/- 0.5 ml.min-1 x 100 g-1) of resting ponies was only one-third of the bronchial blood flow (21.6 +/- 4.9 ml.min-1 x 100 g-1) Significant changes in tracheal perfusion did not occur at 3rd or 10th min of exercise. Although bronchial perfusion also did not change at the 3rd min of exercise, it rose dramatically to 202.8 +/- 30.3 ml.min-1 x 100 g-1 during the 10th min. Concomitantly, renal blood flow decreased at 10th min of exertion. The large increase in bronchial blood flow at 10th min of exertion may have been necessitated by the need to help dissipate body heat.     

Exercise limits the production of endothelin in the coronary vasculature

We previously demonstrated that endothelin (ET)-mediated coronary vasoconstriction wanes with increasing exercise intensity via a nitric oxide- and prostacyclin-dependent mechanism (Ref. 23). Therefore, we hypothesized that the waning of ET coronary vasoconstriction during exercise is the result of decreased production of ET and/or decreased ET receptor sensitivity. We investigated coronary ET receptor sensitivity using intravenous infusion of ET and coronary ET production using intravenous infusion of the ET precursor Big ET, at rest and during continuous treadmill exercise at 3 km/h in 16 chronically instrumented swine. In the systemic vasculature, Big ET and ET induced similar changes in hemodynamic parameters at rest and during continuous exercise at 3 km/h, indicating that exercise does not alter ET production or receptor sensitivity in the systemic vasculature. In the coronary vasculature, infusion of ET resulted in similar dose-dependent decreases in coronary blood flow and coronary venous oxygen tension and saturation at rest and during exercise. In contrast, administration of Big ET resulted in dose-dependent decreases in coronary blood flow, as well as coronary venous oxygen tension and saturation at rest. These effects of Big ET were significantly reduced during exercise. Altogether, our data indicate that continuous exercise at 3 km/h attenuates ET-mediated coronary vasoconstriction through reduced production of ET from Big ET rather than through reduced ET sensitivity of the coronary vasculature. The decreased ET production during exercise likely contributes to metabolic coronary vasodilation.     

Rodent Working Heart Model for the Study of Myocardial Performance and Oxygen Consumption

Isolated working heart models have been used to understand the effects of loading conditions, heart rate and medications on myocardial performance in ways that cannot be accomplished in vivo. For example, inotropic medications commonly also affect preload and afterload, precluding load-independent assessments of their myocardial effects in vivo. Additionally, this model allows for sampling of coronary sinus effluent without contamination from systemic venous return, permitting assessment of myocardial oxygen consumption. Further, the advent of miniaturized pressure-volume catheters has allowed for the precise quantification of markers of both systolic and diastolic performance. We describe a model in which the left ventricle can be studied while performing both volume and pressure work under controlled conditions. In this technique, the heart and lungs of a Sprague-Dawley rat (weight 300-500 g) are removed en bloc under general anesthesia. The aorta is dissected free and cannulated for retrograde perfusion with oxygenated Krebs buffer. The pulmonary arteries and veins are ligated and the lungs removed from the preparation. The left atrium is then incised and cannulated using a separate venous cannula, attached to a preload block. Once this is determined to be leak-free, the left heart is loaded and retrograde perfusion stopped, creating the working heart model. The pulmonary artery is incised and cannulated for collection of coronary effluent and determination of myocardial oxygen consumption. A pressure-volume catheter is placed into the left ventricle either retrograde or through apical puncture. If desired, atrial pacing wires can be placed for more precise control of heart rate. This model allows for precise control of preload (using a left atrial pressure block), afterload (using an afterload block), heart rate (using pacing wires) and oxygen tension (using oxygen mixtures within the perfusate).     

Modulation of cardiovascular response to dynamic exercise by fastigial nucleus

Mongrel dogs (n = 34) were used to record the cardiovascular responses during submaximal exercise-tolerance tests (ETT) before and after the placement of lesions in rostral portions of the cerebellar fastigial nucleus (FN). Sterile surgical procedures were used to implant solid-state pressure transducers into the left ventricle or descending aorta (anesthesia 1% halothane in O2) and multipolar stainless steel electrodes into FN (anesthesia alpha-chloralose 115 mg/kg iv). Heart rate (HR), maximal left ventricular systolic pressure ( LVPmax ) and its first derivative ( dLVP /dt), and mean arterial blood pressure (MAP) were recorded during a motorized treadmill ETT. Electrolytic direct-current or radio-frequency lesions were made through the indwelling FN electrodes, and the ETT was repeated following 10-14 days recovery. Two-way analysis of variance (ANOVA), with repeated measures on one, and one-way ANOVA for simple effects indicated a significant reduction in HR and MAP (P less than 0.01) but not LVPmax and dLVP /dt occurred during exercise as a result of rostral FN lesions. Although the trend for reduced LVPmax and dLVP /dt was also evident, a relatively greater decrease in blood pressure occurred in the peripheral vasculature during exercise. It was concluded that FN acts as a modulator of HR and MAP during dynamic exercise because of the observed deficits, and because FN is known to both send efferent projections to medullary vasomotor areas and receive projections from motor cortex and muscle and joint afferents.     

Effects of gradual coronary artery occlusion and exercise training on gene expression in swine heart

Gradual occlusion (O) of the swine left circumflex coronary artery (LCX) with an ameroid occluder results in complete O within 3 weeks, collateral vessel development, and compensatory hypertrophy. The purpose of this investigation was to determine the independent and combined effects of O and exercise training (E) on gene expression in the swine heart. Adult Yucatan miniature swine were assigned to one of the following groups (n = 6–9/group): sedentary control (S), exercise-trained (E), sedentary swine subjected to LCX occlusion (SO), and exercise-trained swine with LCX occlusion (EO). Exercise consisted of progressive treadmill running conducted 5 d/wk for 16 weeks. Gene expression was studied in myocardium isolated from the collateral-dependent left ventricle free wall (LV) and the collateral-independent septum (SEP) by RNA blotting. E and O each stimulated cardiac hypertrophy independently (p < 0.001) with no interaction. O but not E increased atrial natriuretic factor expression in the LV, but not in the SEP. E decreased the expression of β-myosin heavy chain in the LV, but not in the SEP. E retarded the expression of collagen III mRNA in SEP; but not in the LV. Exercise training and coronary artery occlusion each stimulate cardiac hypertrophy independently and induce different patterns of gene expression.     

Mechanisms of oxygen demand/supply balance in the right ventricle

Few studies have investigated factors responsible for the O2 demand/supply balance in the right ventricle. Resting right coronary blood flow is lower than left coronary blood flow, which is consistent with the lesser work of the right ventricle. Because right and left coronary artery perfusion pressures are identical, right coronary conductance is less than left coronary conductance, but the signal relating this conductance to the lower right ventricular O2 demand has not been defined. At rest, the left ventricle extracts approximately 75% of the O2 delivered by coronary blood flow, whereas right ventricular O2 extraction is only ~50%. As a result, resting right coronary venous PO2 is approximately 30 mm Hg, whereas left coronary venous PO2 is approximately 20 mm Hg. Right coronary conductance does not sufficiently restrict flow to force the right ventricle to extract the same percentage of O2 as the left ventricle. Endogenous nitric oxide impacts the right ventricular O2 demand/supply balance by increasing the right coronary blood flow at rest and during acute pulmonary hypertension, systemic hypoxia, norepinephrine infusion, and coronary hypoperfusion. The substantial right ventricular O2 extraction reserve is used preferentially during exercise-induced increases in right ventricular myocardial O2 consumption. An augmented, sympathetic-mediated vasoconstrictor tone blunts metabolically mediated dilator mechanisms during exercise and forces the right ventricle to mobilize its O2 extraction reserve, but this tone does not limit resting right coronary flow. During exercise, right coronary vasodilation does not occur until right coronary venous PO2 decreases to approximately 20 mm Hg. The mechanism responsible for right coronary vasodilation at low PO2 has not been delineated. In the poorly autoregulating right coronary circulation, reduced coronary pressure unloads the coronary hydraulic skeleton and reduces right ventricular systolic stiffness. Thus, normal right ventricular external work and O2 demand/supply balance can be maintained during moderate coronary hypoperfusion.     

Hemodynamic responses during exercise at and above VO2max in swine

Mean arterial pressure (Pa), heart rate, cardiac output (Q), and Q distribution (with radiolabeled microspheres) were measured in miniature swine as they ran at high levels on a motor-driven treadmill. Each animal ran on two occasions: once during exercise at maximal O2 uptake (VO2max) and once at an intensity estimated to require approximately 115% VO2max. The purpose was to assess these cardiovascular variables to determine whether the calculated resistance to blood flow during supramaximal exercise was different from that during maximal exercise. A total of 114 tissues/organs were dissected for blood flow analysis. Pa and Q were unaltered between the two exercise conditions. Blood flow to all but one of the 62 skeletal muscles sampled was unchanged between conditions as were the blood flows to the visceral organs and brain. The results demonstrate that vascular resistance was constant in all these tissues between maximal and supramaximal exercise intensities. Elevated blood flows were measured in 7 of the 11 coronary sites sampled. Calculated resistance to blood flow indicated that a decrease in resistance occurred in most of the samples having elevated blood flow. Because heart rate was elevated during the supramaximal exercise, the increase in blood flow was probably in response to the greater myocardial work and concomitant elevation in O2 demand. In summary, it was shown that Pa, Q, and Q distribution in most tissues remained unchanged during exercise at intensities above VO2max. Thus a precise matching occurs between the increasingly powerful vasoconstrictor drive initiated by the sympathetic nervous system and the elevated local vasodilatory drive responding to the greater O2 demand during the supramaximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)