Effects of naloxone on systemic and regional hemodynamic responses to exercise in dogs

To determine whether endogenous opiates have a role in circulatory regulation during mild to moderate exercise, 11 chronically instrumented dogs were exercised on a treadmill up a 6% incline at 2.5 and 5.0 mph, each for 20 min, after treatment with either the opiate receptor antagonist naloxone (1 mg/kg bolus and 20 micrograms.kg-1.min-1 infusion) or normal saline. Naloxone increased plasma beta-endorphin and adrenocorticotropic hormone at rest but had no effect on resting heart rate, aortic pressure, cardiac output, left ventricular time derivative of pressure (dP/dt) and ratio of dP/dt at a developed pressure of 50 mmHg and the developed pressure (dP/dt/P), or plasma catecholamines. Plasma beta-endorphin and adrenocorticotropic hormone increased during exercise. In addition, graded treadmill exercise produced proportional increases in heart rate, cardiac output, aortic pressure, left ventricular dP/dt and dP/dt/P, and blood flow to exercising muscles, right and left ventricular myocardium, and adrenal glands. However, there were no differences in the circulatory responses to exercise between animals receiving naloxone and normal saline. Thus the endogenous opiate system probably does not play an important role in regulating the systemic hemodynamic and blood flow responses to mild and moderate exercise.     

Effects of dichloroacetate on hemodynamic responses to dynamic exercise in dogs.

To determine whether lactic acid production contributes significantly to the cardiac responses to muscular dynamic exercise, we administered intravenous sodium dichloroacetate (32 mumol.kg-1.min-1), a pyruvate dehydrogenase activator that facilitates lactate metabolism via the tricarboxylic cycle, in 12 dogs during two graded levels of treadmill exercise. Similar exercise was carried out in nine normal dogs receiving equimolar doses of NaCl. In the latter group, arterial lactate increased progressively from 0.80 +/- 0.11 (SE) mmol/l at rest to 2.13 +/- 0.28 mmol/l by the end of exercise. In contrast, arterial lactate did not change significantly (0.98 +/- 0.12 to 0.95 +/- 0.11 mmol/l) during exercise in dogs receiving dichloroacetate infusion. Dichloroacetate infusion also reduced the increases in plasma norepinephrine, heart rate, and left ventricular contractile indexes that occurred during exercise, suggesting that the sympathetic cardiac stimulation occurring during exercise may be related to the production of lactic acid. However, dichloroacetate affected neither the net increase in cardiac output nor the relationship between total body oxygen consumption and cardiac output that occurred during exercise. Thus we conclude that lactic acid production is not essential to the increase in cardiac output that occurs during mild-to-moderate exercise.     

Altered muscle metaboreflex control of coronary blood flow and ventricular function in heart failure

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF), coronary vascular conductance (CVC), and regional left ventricular performance in conscious, chronically instrumented dogs during treadmill exercise before and after the induction of heart failure (HF). In control experiments, muscle metaboreflex activation during mild exercise elicited significant reflex increases in mean arterial pressure, heart rate, and cardiac output. CBF increased significantly, whereas no significant change in CVC occurred. There was no significant change in the minimal rate of myocardial shortening (-dl/dt(min)) with muscle metaboreflex activation during mild exercise (15.5 +/- 1.3 to 16.8 +/- 2.4 mm/s, P > 0.05); however, the maximal rate of myocardial relaxation (+dl/dt(max)) increased (from 26.3 +/- 4.0 to 33.7 +/- 5.7 mm/s, P < 0.05). Similar hemodynamic responses were observed with metaboreflex activation during moderate exercise, except there were significant changes in both -dl/dt(min) and dl/dt(max). In contrast, during mild exercise with metaboreflex activation during HF, no significant increase in cardiac output occurred, despite a significant increase in heart rate, inasmuch as a significant decrease in stroke volume occurred as well. The increases in mean arterial pressure and CBF were attenuated, and a significant reduction in CVC was observed (0.74 +/- 0.14 vs. 0.62 +/- 0.12 ml x min(-1) x mmHg(-1); P < 0.05). Similar results were observed during moderate exercise in HF. Muscle metaboreflex activation did not elicit significant changes in either -dl/dt(min) or +dl/dt(max) during mild exercise in HF. We conclude that during HF the elevated muscle metaboreflex-induced increases in sympathetic tone to the heart functionally vasoconstrict the coronary vasculature, which may limit increases in myocardial performance.     

Haemodynamic effects of respiratory alkalosis independent of changes in airway pressure in anaesthetized newborn dogs

We have recently reported a decrease in cardiac output in newborn dogs during respiratory alkalosis which is independent of changes in airway pressure. The present study was designed to characterize the mechanism responsible for this reduction in cardiac output. Twelve newborn coonhounds were anaesthetized with pentobarbital, paralyzed with pancuronium and hyperventilated to an arterial carbon dioxide tension (PaCO2) of 20 torr. Subsequent changes in PaCO2 were achieved by altering the FiCO2. Measurements were made after 30 min at either 40 or 20 torr PaCO2. The sequence of PaCO2 levels was randomized. Compared to normocarbia, respiratory alkalosis resulted in significantly decreased cardiac output (279 +/- 16 to 222 +/- 10 ml/min per kg, mean +/- SEM, P less than 0.001), stroke volume (1.60 +/- 0.10 to 1.24 +/- 0.06 ml/kg; P less than 0.001), maximum left ventricular dP/dt (1629 +/- 108 to 1406 +/- 79 mmHg/s, P less than 0.01) and left ventricular end diastolic pressure (3.9 +/- 0.4 to 2.9 +/- 0.3 mmHg; P less than 0.001). The decrease in cardiac output during respiratory alkalosis is manifest through a decrease in stroke volume, which is due, at least in part, to the decrease in left ventricular end diastolic pressure. The decrease in maximum left ventricular dP/dt is likely a reflection of the decrease in preload, however, a change in myocardial contractility cannot be excluded. We speculate the decrease in filling pressure may be due to an increase in venous capacitance.     

Ventilatory control during exercise in calves with artificial hearts

To determine the role of cardiac reflexes in mediating exercise hyperpnea, we investigated ventilatory responses to treadmill exercise in seven calves with artificial hearts and seven controls. In both groups, the ventilatory responses were adequate for the metabolic demands of the exercise; this resulted in regulation of arterial PCO2 and pH despite the absence of cardiac output increase in the implanted group. In this group, there was a small but significant reduction of arterial PO2 by 4 +/- 3 Torr and a rise of blood lactate by 1.1 +/- 1 mmol/l. When cardiac output was experimentally increased in the implanted calves to a level commensurate with that spontaneously occurring in the control calves, ventilation was not affected. However, experimental reductions of cardiac output led to an immediate augmentation of exercise hyperpnea by 4.56 +/- 4.3 l/min and a further significant lactate increase of 1.2 +/- 1.22 mmol/l that was associated with a significant decrease in the exercise O2 consumption (0.32 +/- 0.13 l/min). These observations indicate that neither cardiac nor hemodynamic effects of increased cardiac output constitute an obligatory cause of exercise hyperpnea in the calf.     

Adaptation of the left ventricle to exercise-induced hypertrophy

Cardiac functional and structural adaptations to exercise-induced hypertrophy were studied in 68 pigs. Pigs were exercise trained on a treadmill for 10 wk. Sequential measurements were made of cardiac dimensions, [left ventricular end-diastolic diameter (EDD), changes in diameter (delta D%), wall thickness (WTh), wall thickening (WTh%), left ventricular pressure (LVP), time derivative of pressure (dP/dt), stroke volume, total body O2 consumption (VO2), blood gases, and systemic hemodynamics] at rest and during moderate and severe exercise. Postmortem studies included morphometric measurements of capillary density, arteriolar density, mitochondria, and myofibrils. All of the exercise-trained pigs showed significant increases in aerobic capacity. Maximum O2 consumption (VO2 max) increased by 37.5% in group 1 (moderate exercise training) and 34% in group 3 (heavy exercise training). Cardiac hypertrophy ranged from less than 15% in a group (n = 8) subjected to moderate exercise training to greater than 30% in a group (n = 11) subjected to heavy exercise training. Before training, exercise was characterized by a decreasing EDD during progressive exercise; this was reversed after exercise training. Stroke volume and end-diastolic volumes during exercise showed a highly significant increase after exercise training and hypertrophy. Morphometric measurements showed that mitochondria and cell membranes increased with increasing myocyte growth in all exercise groups, but there was only a partially compensated adaptation of capillary proliferation. Arteriolar number and length increased in all exercise groups. Intrinsic contractility as measured by delta D%, WTh%, or left ventricular dP/dt did not increase with exercise training and in some instances decreased. Therefore, left ventricular adaptation to strenuous exercise in the pig heart is primarily one of changes in left ventricular dimensions and a compensated hypertrophy. Exercise-induced increases in EDD and stroke volume can be accounted for by decreases in peripheral resistance and increased cardiac dimensions.     

Myocardial functional correlates of cardiac myosin light chain 2 phosphorylation

In vitro and in situ studies have proposed a potentiation of submaximal force production after myosin light chain 2 (P-light chain) phosphorylation in mammalian striated muscle. The purpose of this study was to ascertain the relationship between the augmentation in left ventricular pressure development and cardiac myosin P-light chain phosphorylation at different times during and after submaximal treadmill exercise involving adult female Sprague-Dawley rats. In vivo hemodynamic measurements were monitored with an indwelling high-fidelity solid-state pressure transducer. Exercise heart rate, peak left ventricular (LV) pressure, and rate of LV pressure development/relaxation (LV +/- dP/dt) were significantly elevated compared with a normal sedentary group (P less than 0.001). Peak LV pressure remained significantly elevated throughout 20 min of postexercise recovery (P less than 0.01), and heart rate, LV end-diastolic pressure, and LV +/- dP/dt returned rapidly to preexercise values. Corresponding to these in vivo hemodynamic changes, increased levels of P-light chain phosphorylation were observed during both exercise (16%, P less than 0.01) and subsequent recovery periods (14%, P less than 0.02) compared with the NC group. A quasi-temporal relationship was observed between postexercise peak LV pressure potentiation and P-light chain phosphorylation. These results demonstrate that cardiac myosin P-light chain phosphorylation is associated, in part, with the augmentation of peak LV pressure observed during both exercise and recovery.     

Effects of enhanced ventricular filling on cardiac pump performance in exercising dogs

The extent to which the normal increase in stroke volume during exercise can be augmented by increasing preload by dextran infusion was studied in seven dogs. Each dog ran 3 min on a level treadmill at mild (3-4 mph), moderate (6-8 mph), and severe (9-13 mph) loads during the control study and immediately after 10% dextran 14 ml/kg iv. During severe exercise dextran-augmented stroke volume (+5.4 ml or 19% vs. exercise without dextran, P less than 0.01) and left ventricular end-diastolic diameter and pressure did not change heart rate, aortic pressure, or maximum derivative of left ventricular pressure but decreased systemic vascular resistance by 16%. Similar increases in stroke volume and preload after dextran occurred during mild and moderate exercise when arterial pressure and heart rate were unchanged or increased and systemic vascular resistance was decreased. Thus altering preload above those levels normally encountered during exercise is a potential mechanism to increase stroke volume and cardiac output.     

Alteration in myocardial oxygen balance during exercise after beta-adrenergic blockade in dogs

The effects of beta-adrenergic blockade upon myocardial blood flow and oxygen balance during exercise were evaluated in eight conscious dogs, instrumented for chronic measurements of coronary blood flow, left ventricular pressure, aortic blood pressure, heart rate, and sampling of arterial and coronary sinus venous blood. The administration of propranolol (1.5 mg/kg iv) produced a decrease in heart rate, peak left ventricular (LV) dP/dt, LV (dP/dt/P, and an increase in LV end-diastolic pressure during exercise. Mean coronary blood flow and myocardial oxygen consumption were lower after propranolol than at the same exercise intensity in control conditions. The oxygen delivery-to-oxygen consumption ratio and the coronary sinus oxygen content were also significantly lower. It is concluded that the relationship between myocardial oxygen supply and demand is modified during exercise after propranolol, so that a given level of myocardial oxygen consumption is achieved with a proportionally lower myocardial blood flow and a higher oxygen extraction.     

Function of mature coronary collateral vessels and cardiac performance in the exercising dog

Formation of extensive collateral vessels after chronic constriction of a coronary artery in dogs can provide for similar increases in blood flow to native and collateralized regions of myocardium during exertion. Previous investigations have not compared myocardial blood flow and cardiac functional responses during exercise in constricted and nonconstricted (sham) animals. Thus we evaluated left ventricular performance and myocardial blood flow at rest and during mild, moderate, and severe exertion in sham-operated dogs and in dogs 2-3 mo after placement of an Ameroid occluder around the proximal left circumflex artery. Changes in double product, maximal left ventricular dP/dt, and pressure-work index were similar in both groups for each level of exertion. Despite similar increases in estimated myocardial O2 demand and similar diastolic perfusion pressures, average transmural myocardial blood flow increased less in the constrictor animals, particularly during severe exercise (2.74 +/- 0.22 vs. 1.45 +/- 0.29 ml X min-1 X g-1). The smaller increases in blood flow occurred equally in native and collateralized regions as well as in the papillary muscles and boundary areas between the native and collateralized regions. The differences in flow in the native and collateralized regions were uniform across the wall of the myocardium. We also observed smaller increases in stroke volume and cardiac output in the constrictor group, disparities which increased with increasing exertion (stroke volume, severe exercise = 0.92 +/- 0.13 vs. 0.53 +/- 0.09 ml/kg). We postulate that myocardial active hyperemia is limited either because the coronary vessels remaining after chronic circumflex occlusion cannot dilate sufficiently or that there is inappropriate active vasoconstriction during severe exertion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat.

These experiments examined the independent effects of short-term exercise and heat stress on myocardial responses during in vivo ischemia-reperfusion (I/R). Female Sprague-Dawley rats (4 mo old) were randomly assigned to one of four experimental groups: 1) control, 2) 3 consecutive days of treadmill exercise [60 min/day at 60-70% maximal O2 uptake (VO2 max)], 3) 5 consecutive days of treadmill exercise (60 min/day at 60-70% VO2 max), and 4) whole body heat stress (15 min at 42 degrees C). Twenty-four hours after heat stress or exercise, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was maintained for 30-min followed by a 30-min period of reperfusion. Compared with control, both heat-stressed animals and exercised animals (3 and 5 days) maintained higher (P < 0.05) left ventricular developed pressure (LVDP), maximum rate of left ventricular pressure development (+dP/dt), and maximum rate of left ventricular pressure decline (-dP/dt) at all measurement periods during both ischemia and reperfusion. No differences existed between heat-stressed and exercise groups in LVDP, +dP/dt, and -dP/dt at any time during ischemia or reperfusion. Both heat stress and exercise resulted in an increase (P < 0.05) in the relative levels of left ventricular heat shock protein 72 (HSP72). Furthermore, exercise (3 and 5 days) increased (P < 0.05) myocardial glutathione levels and manganese superoxide dismutase activity. These data indicate that 3-5 consecutive days of exercise improves myocardial contractile performance during in vivo I/R and that this exercise-induced myocardial protection is associated with an increase in both myocardial HSP72 and cardiac antioxidant defenses.     

Comparison of exercise effects on the hemodynamics of the Bio 14.6 cardiomyopathic hamster.

1. Comparisons of the effects of 4 and 16 weeks of exercise were made on; cardiac output, stroke volume, heart rate, left intraventricular systolic and diastolic pressures, dP/dt, and heart calcium in the Bio 14.6 cardiomyopathic and F1 B hamsters. 2. In the cardiomyopathic hamster the cardiac output, stroke volume, left intraventricular systolic pressure and dP/dt, which were all depressed in the age related sedentary animals, were increased by both periods of exercise. The left intraventricular diastolic pressure which was elevated was likewise decreased by both exercise periods. Only the 16 week exercise period decreased the resting heart rate. 3. In the normal F1 B hamster, both periods of exercise increased the cardiac output and stroke volume while the left intraventricular systolic pressure was decreased. Only the 16 week exercise decreased the resting heart rate and left intraventricular diastolic pressure and increased the left ventricular dP/dt. 4. Both periods of exercise increased the total heart calcium in the Bio 14.6 hamster while the heart calcium in the F1 B was increased only by the 16 week exercise period.     

Chronic exercise training preserves prostaglandin-induced dilation of epicardial coronary artery during development of heart failure in awake dogs

Although it has been shown that long-term exercise training preserves endothelium-mediated nitric oxide vasodilator function in chronic heart failure (CHF), whether exercise training exerts similar beneficial effects on endothelial/prostaglandin-mediated vasodilator capacity in coronary circulation during the development of CHF has not been determined. Fifteen mongrel dogs were surgically instrumented for measurement of left ventricular pressure, aortic pressure, coronary blood flow and left circumflex coronary artery diameter. Dogs (n = 5) who underwent 4 weeks of cardiac pacing (210 b/min for 3 weeks and 240 b/min for the 4th week) developed CHF as characterized by significant reduction in left ventricular systolic pressure, mean arterial pressure and left ventricular dP/dt, increases in left ventricular end-diastolic pressure and heart rate, as well as clinical signs of CHF. Endothelial prostaglandin-mediated vasodilation of the epicardial coronary artery was impaired, as manifested by an attenuated arachidonic acid (AA)-induced dilation of the artery (epicardial artery diameter increased by: 0.78 +/- 0. 84% in CHF versus 4.6 +/- 0.89% in normal, P < 0.05); however, prostacyclin (PGI(2))-induced and nitroglycerin-induced vasodilation of the coronary circulation were not altered. In contrast, dogs (n = 6) with cardiac pacing plus daily exercise training (4.4 +/- 0.3 km/h, 2 h/day) only developed mild cardiac dysfunction, and the response of the epicardial coronary artery diameter to AA was preserved (epicardial artery diameter increased by 4.2 +/- 0.98% from baseline, P 0.05 compared to its respective control). Thus, long-term exercise training preserves endothelial/prostaglandin-mediated dilation of epicardial coronary artery during development of CHF.     

Cardiac responsiveness to beta-adrenergic stimulation in experimental anemia.

Cardiac reactivity of beta-adrenergic stimulation was assessed by isoproterenol dose-reponse curves (dose range 0.025-0.4 mug/kg) before and 1 h after the rapid induction of anemia in dogs anesthetized with halothane:N2O:O2. Anemai (hematocrit = 16 +/- 4%) was induced by an isovolumic exchange transfusion with Dextran 70, and was followed by significant increments in cardiac output (+57 +/- 9%), max dP/dt of the left ventricle (+37 +/- 7%), and in peak acceleration of blood flow in the ascending aorta (+46 +/- 13%). Anemia was associated with a significant reduction of the chronotropic responses to all but the lowest dose of isoproterenol. The simultaneously determined inotropic responses (max dP/dt) where the same before and after the induction of anemia. The responses in terms of peak acceleration of aortic blood flow tended to be greater in the anemic than in the control phase, at all dose levels used. These findings indicate that in rapidly induced experimental anemia the heart is capable of responding to marked degrees of beta-adrenergic stimulation, representing a more than two-fold increase in the dP/dt.     

Effect of PDE5 inhibition on coronary hemodynamics in pacing-induced heart failure

Inhibition of phosphodiesterase type 5 (PDE5) can relax systemic and coronary vessels by causing accumulation of cGMP. Both the endothelial dysfunction with decreased nitric oxide production and increased natriuretic peptide levels in congestive heart failure (CHF) have the potential to alter cGMP production, thereby influencing the response to PDE5 inhibition. Consequently, this study examined the effects of PDE5 inhibition with sildenafil in dogs with CHF produced by rapid ventricular pacing. CHF resulted in decreases of left ventricular (LV) systolic pressure, coronary blood flow, and the maximal first time derivative of LV pressure (LV dP/dt(max)) at rest and during treadmill exercise compared with normal, whereas resting LV end-diastolic pressure increased from 10 +/- 1.4 to 23 +/- 1.4 mmHg. Sildenafil (2 and 10 mg/kg per os) caused a 5- to 6-mmHg decrease of aortic pressure (P < 0.05), with no change of heart rate, LV systolic pressure, or LV dP/dt(max). Sildenafil caused no change in coronary flow or myocardial oxygen consumption in animals with CHF at rest or during exercise. In contrast to findings in normal animals, sildenafil did not augment endothelium-dependent coronary vasodilation in response to acetylcholine in animals with CHF. Furthermore, Western blotting showed decreased PDE5 protein expression in myocardium from failing hearts. These findings demonstrate that PDE5 contributes little to regulation of coronary hemodynamics in CHF.     

Bradykinin-induced chemoreflexes from skeletal muscle: implications for the exercise reflex

We examined the cardiovascular response to bradykinin stimulation of skeletal muscle afferents and the effect of prostaglandins on this response. Intra-arterial injection of 1 microgram bradykinin into the gracilis muscle of cats reflexly increased mean arterial pressure by 16 +/- 2 mmHg, left ventricular end-diastolic pressure by 1.6 +/- 0.6 mmHg, maximal dP/dt by 785 +/- 136 mmHg/s, heart rate by 11 +/- 2 beats/min, and mean aortic flow by 22 +/- 3 ml/min. The hemodynamic responses were abolished following denervation of the gracilis muscle. The increases in mean arterial pressure and maximal dP/dt were reduced by 68 and 45%, respectively, following inhibition of prostaglandin synthesis with indomethacin (2-8 mg/kg iv). Treatment with prostaglandin E2 (PGE2, 15-25 micrograms ia) restored the initial increase in mean arterial pressure, but not dP/dt, caused by bradykinin stimulation. Injection of PGE2 (15-30 micrograms ia) into the gracilis, without prior treatment with indomethacin, augmented the bradykinin-induced increases in mean arterial pressure and dP/dt. We conclude that small doses of bradykinin injected into skeletal muscle are capable of reflexly activating the cardiovascular system and that prostaglandins are necessary for the full manifestation of the corresponding hemodynamic response. The pattern of hemodynamic adjustment following bradykinin injection into skeletal muscle is very similar to that induced by static exercise. Therefore, it is possible that intense exercise provides a stimulus for this bradykinin-induced reflex in vivo.     

Neurohumoral and cardiopulmonary response to sustained submaximal exercise in the dog

Neurohumoral, cardiovascular, and respiratory parameters were evaluated during sustained submaximal exercise (3.2 km/h, 15 degrees elevation) in normal adult mongrel dogs. At the level of activity achieved (fivefold elevation of total body O2 consumption and threefold elevation of cardiac output), significant (P less than 0.05) increases in plasma norepinephrine and epinephrine concentration (from 150 +/- 23 to 341 +/- 35 and from 127 +/- 27 to 222 +/- 31 pg/ml, respectively) were present, as well as smaller but significant increases in plasma renin activity and plasma aldosterone concentration (from 2.2 +/- 0.3 to 3.1 +/- 0.6 ng X ml-1 X h-1 and from 98 +/- 8 to 130 +/- 6 pg/ml, respectively). Plasma arginine vasopressin increased variably and insignificantly. The cardiovascular response (heart rate, systemic arterial and pulmonary arterial pressures, left ventricular filling pressure, and calculated total peripheral and pulmonary arteriolar resistance) closely paralleled that of human subjects. Increased hemoglobin concentration was induced by exercise in the dogs. The ventilatory response of the animals was characterized by respiratory alkalosis. These data suggest similarities between canine and human subjects in norepinephrine, plasma renin activity, and plasma aldosterone responses to submaximal exercise. Apparent species differences during submaximal exertion include greater alterations of plasma epinephrine concentration and a respiratory alkalosis in dogs.     

Gender differences on the effects of aging on cardiac and peripheral adrenergic stimulation in old conscious monkeys

We examined the effects of gender and aging on cardiac and peripheral hemodynamic responses to beta-adrenergic receptor (beta-AR) stimulation in young (male = 5.9 +/- 0.4 yr old and female = 6.5 +/- 0.7 yr old) and old (male = 19.8 +/- 0.7 yr old and female = 21.2 +/- 0.2 yr old) conscious monkeys (Macaca fascicularis), chronically instrumented for measurements of left ventricular (LV) and arterial pressures as well as cardiac output. Baseline LV pressure, the first derivative of LV pressure (LV dP/dt), cardiac index, mean arterial pressure, total peripheral resistance (TPR), and heart rate in conscious monkeys were not different among the four groups. Increases in LV dP/dt in response to 0.1 microg/kg isoproterenol (Iso) were diminished (P < 0.05) in old males (+99 +/- 11%) compared with young males (+194 +/- 18%). In addition, the inotropic responses to norepinephrine (NE) and forskolin (FSK) were significantly depressed (P < 0.05) in old males. Iso-induced reductions of TPR were less (P < 0.05) in old males (-28 +/- 2%) than in young males (-49 +/- 2%). The changes of TPR in response to NE and FSK were also significantly attenuated (P < 0.05) in old males. However, the LV dP/dt responses to BAY y 5959 (15 microg. kg-1. min-1), a Ca2+ channel promotor independent of beta-AR signaling, were not significantly different between old and young males. In contrast to results in male monkeys, LV dP/dt and TPR responses to Iso, NE, and FSK in old females were similar to those observed in young females. Thus both cardiac contractile and peripheral vascular dynamic responses to beta-AR stimulation are preserved in old female but not old male monkeys. This may explain, in part, the reduced cardiovascular risk in the older female population.     

Regulation of oxygen delivery during induced polycythemia in exercising dogs

Previous studies have concluded that polycythemia decreases oxygen delivery primarily because of a large fall in cardiac output associated with a rise in systemic vascular resistance that has been attributed to increased blood viscosity. However, because other studies have shown that polycythemia may not reduce oxygen delivery, an alternative hypothesis is that cardiac output falls in response to a rising oxygen content, thereby maintaining oxygen delivery constant. To determine whether oxygen content participates in the regulation of cardiac output during polycythemia, we studied eight chronically instrumented dogs trained to exercise on a treadmill. The dogs underwent exchange transfusion with packed red blood cells containing methemoglobin, which caused an increase in hematocrit from 35 +/- 1 to 50 +/- 1% and in viscosity, with little change in oxygen content. The expected fall in exercise cardiac output failed to occur after exchange transfusion with red blood cells containing methemoglobin (7.5 +/- 4 vs. 6.8 +/- 0.5 l/min; P = not significant), and there was no rise in systemic vascular resistance. Methylene blue was then administered intravenously to facilitate conversion of methemoglobin to oxyhemoglobin, which increased oxygen content (12.8 +/- 0.9 vs. 18.4 +/- 0.9 vol%; P < 0.01) with no change in hematocrit or viscosity. Resting cardiac output did not change significantly, but there was a significant decrease in exercise output (6.8 +/- 0.5 vs. 5.8 +/- 0.4 l/min; P < 0.05). Thus we conclude that the fall in cardiac output seen in acute polycythemia results in part from the regulation of oxygen delivery and is not due solely to increased blood viscosity.     

Costal vs. crural diaphragmatic blood flow during submaximal and near-maximal exercise in ponies

The present study was carried out 1) to compare blood flow in the costal and crural regions of the equine diaphragm during quiet breathing at rest and during graded exercise and 2) to determine the fraction of cardiac output needed to perfuse the diaphragm during near-maximal exercise. By the use of radionuclide-labeled 15-micron-diam microspheres injected into the left atrium, diaphragmatic and intercostal muscle blood flow was studied in 10 healthy ponies at rest and during three levels of exercise (moderate: 12 mph, heavy: 15 mph, and near-maximal: 19-20 mph) performed on a treadmill. At rest, in eucapnic ponies, costal (13 +/- 3 ml.min-1.100 g-1) and crural (13 +/- 2 ml.min-1.100 g-1) phrenic blood flows were similar, but the costal diaphragm received a much larger percentage of cardiac output (0.51 +/- 0.12% vs. 0.15 +/- 0.03% for crural diaphragm). Intercostal muscle perfusion at rest was significantly less than in either phrenic region. Graded exercise resulted in significant progressive increments in perfusion to these tissues. Although during exercise, crural diaphragmatic blood flow was not different from intercostal muscle blood flow, these values remained significantly less (P less than 0.01) than in the costal diaphragm. At moderate, heavy, and near-maximal exercise, costal diaphragmatic blood flow (123 +/- 12, 190 +/- 12, and 245 +/- 18 ml.min-1.100 g-1) was 143%, 162%, and 162%, respectively, of that for the crural diaphragm (86 +/- 10, 117 +/- 8, and 151 +/- 14 ml.min-1.100 g-1).(ABSTRACT TRUNCATED AT 250 WORDS)