Leg vasoconstriction during dynamic exercise with reduced cardiac output.

We evaluated whether a reduction in cardiac output during dynamic exercise results in vasoconstriction of active skeletal muscle vasculature. Nine subjects performed four 8-min bouts of cycling exercise at 71 +/- 12 to 145 +/- 13 W (40-84% maximal oxygen uptake). Exercise was repeated after cardioselective (beta 1) adrenergic blockade (0.2 mg/kg metoprolol iv). Leg blood flow and cardiac output were determined with bolus injections of indocyanine green. Femoral arterial and venous pressures were monitored for measurement of heart rate, mean arterial pressure, and calculation of systemic and leg vascular conductance. Leg norepinephrine spillover was used as an index of regional sympathetic activity. During control, the highest heart rate and cardiac output were 171 +/- 3 beats/min and 18.9 +/- 0.9 l/min, respectively. beta 1-Blockade reduced these values to 147 +/- 6 beats/min and 15.3 +/- 0.9 l/min, respectively (P < 0.001). Mean arterial pressure was lower than control during light exercise with beta 1-blockade but did not differ from control with greater exercise intensities. At the highest work rate in the control condition, leg blood flow and vascular conductance were 5.4 +/- 0.3 l/min and 5.2 +/- 0.3 cl.min-1.mmHg-1, respectively, and were reduced during beta 1-blockade to 4.8 +/- 0.4 l/min (P < 0.01) and 4.6 +/- 0.4 cl.min-1.mmHg-1 (P < 0.05). During the same exercise condition leg norepinephrine spillover increased from a control value of 2.64 +/- 1.16 to 5.62 +/- 2.13 nM/min with beta 1-blockade (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms mediating canine renal vasoconstriction induced by nicotine infusion

We investigated the respective contributions of the renin-angiotensin and alpha-adrenergic systems to nicotine-induced, canine, renal vasoconstriction by using saralasin (4 micrograms/kg/min) and phentolamine (25 micrograms/kg/min) blockade respectively. Nicotine infusion (0.024 mg/kg/min) increased mean arterial blood pressure (MABP) (114 +/- 3.0 to 219 +/- 8.0 mmHg) and decreased total renal blood flow (TRBF) (3.12 +/- 0.34 to 1.60 +/- 0.37 ml/min/g). Nicotine infusion produced a significantly lesser blood flow in outer cortex (OC), inner cortex (IC), and outer medulla (OM) compared to control dogs. The intrarenal-artery infusion of saralasin or phentolamine had no effect on the nicotine-induced MABP changes. Phentolamine infusion prior to nicotine resulted in a significantly greater TRBF (P less than 0.01), OC (p less than 0.001), IC (p less than 0.001) and OM (p less than 0.01) flow than in the group that received nicotine only. Saralasin pretreatment prior to nicotine resulted only in a significantly (p less than 0.01) greater OC flow than nicotine only. Our data suggest that while angiotensin II mediates a portion of the action of nicotine on the OC renal vasculature, the alpha adrenergic system predominates as the mediator of nicotine-induced renal vasoconstriction in the first 7 minutes of nicotine infusion.     

Blood pressure and metabolic effects of 18-oxo-cortisol in sheep

18-Oxo-cortisol (18-oxo-F) has been isolated from the urine of subjects with primary aldosteronism. This study examines the pressor, mineralocorticoid and glucocorticoid effects of 18-oxo-F in conscious sheep--a well studied species for the assessment of the pressor effect of steroid hormones. 18-oxo-F (24 mg/day i.v. for 5 days, n = 3) increased mean arterial pressure MAP (64 +/- 2 mmHg control and 75 +/- 6 mmHg on day 5 P less than 0.001). There was no change in heart rate. Plasma [K+] decreased from a control of 4.3 +/- 0.1 mmol/l control to 2.9 +/- 0.3 mmol/l on day 5 (P less than 0.001). Urinary Na+ excretion decreased on the first infusion day (233 +/- 18 mmol/day control and 124 +/- 20 mmol/day on infusion day 1 P less than 0.001). Urinary K+ excretion was reduced on days 1, 4 and 5 of the infusion. Thus in sheep, 18-oxo-F increased blood pressure associated with in vivo evidence of mineralocorticoid activity.     

Effects of chronic and acute exercise on cardiovascular beta-adrenergic responses.

beta-Adrenergic receptor density and responsiveness may be increased in experimental animals by physical conditioning, and the opposite effects have been observed after a single bout of exercise. To determine whether the chronic and acute effects of exercise include similar alterations in cardiovascular function in humans, we characterized heart rate, blood pressure, and distal lower extremity blood flow responses to graded-dose isoproterenol infusion in 15 young healthy subjects before and after exercise training and with and without a single preceding bout of prolonged exercise of either low or high intensity (61 +/- 1 or 82 +/- 1% maximal heart rate). VO2max was increased 18% after exercise training (43.2 +/- 2.7 to 51.1 +/- 3.3 ml.kg-1.min-1; P less than 0.001). Despite a concomitant fall in resting heart rate (59 +/- 3 to 50 +/- 2 beats/min; P less than 0.001), chronotropic and lower extremity blood flow responses to isoproterenol remained unchanged. Similarly, 1 h of acute high-intensity treadmill exercise altered baseline heart rate (58 +/- 4 to 74 +/- 5 beats/min; P less than 0.02), but neither low- nor high-intensity acute exercise influenced heart rate or lower extremity blood flow responses to isoproterenol. In contrast, the systolic pressure response to isoproterenol was blunted after high- but not low-intensity prolonged exercise (P less than 0.02). These data indicate that cardiac chronotropic (primarily beta 1) and vascular (beta 2) adrenergic agonist responses are not altered in humans by training or acute exercise. The systolic blood pressure response to beta-adrenergic stimulation is decreased by a single bout of high-intensity prolonged exercise by mechanisms that remain to be defined.     

Vasodepressor reaction induced by inferior vena caval occlusion and isoproterenol.

Testing for the susceptibility for vasodepressor reaction in humans involves the combination of restriction of venous return by passive upright tilting and the administration of isoproterenol. To explore the basis of the vasodepressor test in humans, the present experiment examined whether a reduced cardiac volume coupled with adrenergic stimulation causes a vasodepressor reaction in rats. Vasodepressor reaction was defined as paradoxical heart rate slowing in conjunction with hypotension during inferior vena caval occlusion. Inferior vena caval occlusion was performed for 60 s and the maximum changes in R-R were measured during seven states as follows. (A) Under control conditions inferior vena caval occlusion alone accelerated the rate in 32 of 32 rats (delta R-R, -13.9 +/- 1.7 ms, p less than 0.001). (B) When inferior vena caval occlusion was performed during an infusion of isoproterenol (0.5-1.0 micrograms.min-1), a vasodepressor reaction was observed in all rats as the heart rate slowed (delta R-R, +138.1 +/- 14.8 ms, p less than 0.001). The vasodepressor reaction was further examined during isoproterenol and inferior vena caval occlusion under five additional states. (C) After atropine the vasodepressor reaction was unchanged (delta R-R, +132.7 +/- 24.8 ms, p less than 0.001). (D) After bilateral vagotomy the paradoxical slowing was eliminated. (E) After intrapericardial lidocaine the paradoxic slowing was eliminated. (F) After bilateral stellectomy nonsignificant slowing was still present, but this was markedly reduced when compared with B (p less than 0.001). (G) Following chronic chemical sympathetic denervation with 6-hydroxydopamine the paradoxic bradycardia was eliminated. Conclusions: (1) Reduced cardiac volume combined with adrenergic stimulation can stimulate a vasodepressor reaction; (2) the vasodepressor reaction requires signalling by the afferent but not efferent vagal fibers; (3) the bradycardia is mainly due to withdrawal of sympathetic efferent tone.     

Effects of acute hypercapnia upon the myocardium: contractility, coronary resistance, oxygen consumption and potassium balance (author's transl)

In the isolated perfused dog heart, at constant coronary blood flow and heart rate, we studied the effect of altering CO2 in the gas mixture from 5 to 15% on contractility, coronary resistance, myocardial O2 consumption and K balance. Contractility, assessed by the developed force, and its derivative through a strain-gauge arch sewed to the left ventricle decreased to 54 +/- 7% (p less than 0.01) and 59 +/- 6% (p less than 0.01), respectively from control values. Coronary resistance decreased to 79 +/- 3% of control ( less than 0.01). The negative inotropic effect of hypercapnia was accompanied by a decrease in myocardial O2 consumption to 68 +/- 11% (p less than 0.01) of control value and a net uptake of K by the heart. The possibility of an exchange of H+ by K+ is suggested as a possible mechanism involved in the negative inotropic effect of hypercapnia.     

Changes in diastolic coronary resistance during submaximal exercise in conditioned dogs

Diastolic coronary resistance (DCR) was studied in 10 conscious dogs in the untrained (UT) and partially trained (PT) condition. The PT regime consisted of treadmill running 5 days/wk for 4-5 wk. Left circumflex coronary flow, aortic pressure, and heart rate were measured, and diastolic coronary resistance (DCR) was calculated. Adrenergic blockade was achieved with propranolol (1 mg/kg, iv) (beta B) and phentolamine (1 mg/kg, iv) (alpha B). During submaximal exercise in the UT condition, DCR fell from a resting value of 3.84 +/- 0.24 Torr . ml-1 . min with increasing work load to 1.57 +/- 0.12 Torr . ml-1 . min at 6.4 km/h (speed)/16% (grade). The decrease in DCR during submaximal exercise was greater in the PT than in the UT condition. DCR following alpha-adrenergic blockade was not significantly changed in the UT and PT conditions (e.g., at 6.4 km/h (speed)/16% (grade), 1.10 +/- 0.141 vs. 1.03 +/- 0.107 Torr . ml-1 . min, whereas following beta-adrenergic blockade, DCR was larger in the UT compared with the PT condition (e.g., at 6.4 km/h (speed)/16% (grade), 2.03 +/- 0.091 vs. 1.73 +/- 0.073 Torr . ml-1 X min). Myocardial oxygen consumption was not significantly different in the PT and UT conditions, indicating no difference in metabolism with partial training. The present study suggests that during submaximal exercise in the PT condition there is a change in the neurogenic control of the coronary vasculature by a reduction in sympathetic neural activity on the coronary resistance vessels.     

The protective effect of vagus nerve stimulation on catecholamine-halothane-induced ventricular fibrillation in dogs

Parasympathetic neural activity modulates some ventricular arrhythmias in man. Therefore, a canine model of arrhythmias produced by the interaction of halothane and catecholamines was used to study the effects of vagal stimulation on the induction of ventricular fibrillation. The dose of catecholamine required to induce ventricular fibrillation was determined during a constant heart rate. Vagal stimulation reversibly raised the norepinephrine dose that produced ventricular fibrillation from 16.4 +/- 2.4 to 30.0 +/- 3.8 micrograms (p less than 0.001, n = 10), and the epinephrine dose from 15.5 +/- 2.0 to 22.5 +/- 2.6 micrograms (p less than 0.001, n = 5). Following atropine, vagal stimulation failed to raise the threshold dose of norepinephrine (16.8 +/- 2.4 vs. 18.3 +/- 3.3 micrograms, nonsignificant, n = 6) or epinephrine (15.5 +/- 2.0 vs. 16.0 +/- 2.3 micrograms, nonsignificant, n = 5). Ligation of the cervical vagus nerves did not affect the epinephrine threshold dose (16.3 +/- 3.3 vs. 17.5 +/- 2.7 micrograms, nonsignificant, n = 5). Following elevation of basal vagal tone by morphine premedication, the norepinephrine threshold of 53.0 +/- 9.2 micrograms declined by a nonsignificant amount to 46.5 +/- 11.5 micrograms after vagotomy (nonsignificant, n = 5). Thus resting vagal tone does not prevent catecholamine-halothane-induced ventricular fibrillation, whereas increasing vagal tone by electrical stimulation substantially protects against this arrhythmia. The protection is mediated through a muscarinic cholinergic receptor.     

Diastolic pressure determines autonomic responses to pressure perturbation in humans

Arterial baroreceptors reflexly regulate sympathetic and heart rate responses to alteration of blood pressure. The primary mechanical determinant of arterial baroreceptor activity in humans remains unclear. We examined the influence of systolic, diastolic, pulse, and mean arterial pressures on efferent muscle sympathetic nerve activity (MSNA, microneurography) and heart rate responses during perturbation of arterial pressure in 10 normal human subjects [age 25 +/- 2 (SE) yr]. We directly measured arterial pressure, heart rate, and MSNA during intravenous vasodilator infusion (nitroprusside, 6 +/- 1 micrograms.kg-1.min-1, n = 6; or hydralazine, 16 +/- 2 mg, n = 4) while central venous pressure was held constant by simultaneous volume expansion. Changes in arterial pressures were compared with changes in heart rate and MSNA over 3-min periods of vasodilator infusion during which we observed increases in systolic and pulse pressures with simultaneous decreases in mean and diastolic pressures. During vasodilator infusion, there were increases in systolic (124.2 +/- 2.1 to 131.7 +/- 2.9 Torr, P less than 0.001) and pulse pressures (57.0 +/- 2.2 to 72.7 +/- 2.7 Torr, P less than 0.001) although mean arterial pressure fell (88.0 +/- 2.6 to 80.4 +/- 2.7 Torr, P less than 0.001) because of decreases in diastolic pressure (67.2 +/- 3.0 to 59.0 +/- 2.7 Torr, P less than 0.001). The changes in arterial pressures were accompanied by simultaneous increases in heart rate (66.4 +/- 3.0 to 92.6 +/- 4.8 beats/min, P less than 0.001) and MSNA (327 +/- 59 to 936 +/- 171 U, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional myocardial O2 consumption and coronary blood flow responses to acetylcholine in rabbit heart

The effect of acetylcholine on regional coronary blood flow and myocardial O2 consumption was determined in order to compare its direct vasodilatory effects with the metabolic vasoconstriction it induces. Experiments were conducted in seven untreated control anaesthetized open chest rabbits and seven rabbits which were infused with acetylcholine (1 microgram/kg/min). Myocardial blood flow was determined before and during acetylcholine infusion using radioactive microspheres. Regional arterial and venous O2 saturation was analyzed microspectrophotometrically. Acetylcholine reduced heart rate by 30% and significantly depressed the arterial systolic and diastolic blood pressure. The mean O2 consumption was significantly reduced with acetylcholine from 9.6 +/- 2.0 to 6.1 +/- 3.6 ml O2/min/100 g. Coronary blood flow decreased uniformly across the left ventricular wall by about 50% and resistance to flow increased by 42% despite potential direct cholinergic vasodilation. O2 extraction was not affected by acetylcholine infusion. It is concluded that the acetylcholine infusion directly decreased myocardial O2 consumption, which in turn lowered the coronary blood flow and increased the resistance. The decreased flow was related to a reduced metabolic demand rather than a direct result of lowered blood pressure. Unaffected myocardial O2 extraction also suggested that blood flow and metabolism were matched. This indicates that direct cholinergic vasodilation of the coronary vasculature does not allow a greater reduction in metabolism than flow in the anaesthetized open chest rabbit heart during acetylcholine infusion.     

Difference in the relation between infarct and occluded bed in pentobarbital-anesthetized and conscious dogs

The relationship between myocardial infarct size (IS) and occluded bed size (OBS) in pentobarbital-anesthetized (A, n = 16) and conscious (C, n = 20) dog models were compared. IS and OBS (postmortem coronary arteriography) were measured by computerized planimetry of weighed left ventricular (LV) rings 7 days after permanent left anterior descending (LAD, n = 19) or circumflex (LC, n = 17) coronary artery occlusion. For both A and C groups, IS was directly related to OBS (p less than 0.001) and no infarcts developed for small occluded beds. For either LAD or LC subgroups, infarcts were larger in A than C dogs (49 +/- 18 vs. 30 +/- 19% OBS, p less than 0.025), with greater slope of the linear regression between IS and OBS (p less than 0.001) and less epicardial sparing on topographic mapping (p less than 0.05). Although postocclusion mean arterial and left atrial pressures were similar in A and C groups, heart rates were greater in the A dogs, both pre- (125 vs. 88 beats/min, p less than 0.001) and post-occlusion (151 vs. 108 beats/min, p less than 0.001). Endocardial flows (radioactive microspheres) in infarct centers and margins were less in A than C dogs. Also, endocardial/epicardial (endo/epi) flow ratios in all regions were less in A than C dogs, both pre- and post-occlusion. Increasing heart rate in 10 other C dogs with LAD occlusion to that of the A group (151 beats/min) by right ventricular pacing resulted in larger infarcts with greater slope of the linear regression and less endo/epi flow ratios, as in the A group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic factor attenuates the pulmonary pressor response to hypoxia

The influence of endogenous and exogenous atrial natriuretic factor (ANF) on pulmonary hemodynamics was investigated in anesthetized pigs during both normoxia and hypoxia. Continuous hypoxic ventilation with 11% O2 was associated with a uniform but transient increase of plasma immunoreactive (ir) ANF that peaked at 15 min. Plasma irANF was inversely related to pulmonary arterial pressure (Ppa; r = -0.66, P less than 0.01) and pulmonary vascular resistance (PVR; r = -0.56, P less than 0.05) at 30 min of hypoxia in 14 animals; no such relationship was found during normoxia. ANF infusion after 60 min of hypoxia in seven pigs reduced the 156 +/- 20% increase in PVR to 124 +/- 18% (P less than 0.01) at 0.01 microgram.kg-1.min-1 and to 101 +/- 15% (P less than 0.001) at 0.05 microgram.kg-1.min-1. Cardiac output (CO) and systemic arterial pressure (Psa) remained unchanged, whereas mean Ppa decreased from 25.5 +/- 1.5 to 20.5 +/- 15 mmHg (P less than 0.001) and plasma irANF increased two- to nine-fold. ANF infused at 0.1 microgram.kg-1.min-1 (resulting in a 50-fold plasma irANF increase) decreased Psa (-14%) and reduced CO (-10%); systemic vascular resistance (SVR) was not changed, nor was a further decrease in PVR induced. No change in PVR or SVR occurred in normoxic animals at any ANF infusion rate. These results suggest that ANF may act as an endogenous pulmonary vasodilator that could modulate the pulmonary pressor response to hypoxia.     

Effect of sucrose diet on insulin secretion in vivo and in vitro and on triglyceride storage and mobilisation of the heart of rats

Basal heart triacylglycerol (TG) (mumole triacylglycerol/g of dry weight) (- before "in vitro" Langendorff perfusion -) was significantly higher in animals rendered chronically hypertriglyceridaemic (H) by a 63% sucrose-rich diet than in controls (C, standard diet); 28 +/- 2.6 means + SEM vs. 19.3 +/- 1.2; respectively (p less than 0.01). After 40' perfusion with Krebs-Henseleit buffer + 5.5 mM glucose, 2.5 mM Ca++, TG content fell to 14.2 +/- 0.6 in C and 14.9 +/- 1.9 in H (n.S.). Administration of 1 n mol x min-1 of glucagon (Gn) from min 20 to 40 reduced TG to 9.0 +/- 0.5 in C (p less than 0.05). In contrast no effect of Gn was observed in H (TG at min 40: 16.7 +/- 2.5). Glycogen (Gly) content (mumol/g of dry weight) after Gn perfusion fell from 30 +/- 1.9 to 17 +/- 2.1 (p less than 0.01) in C, while again no effect was recorded in H. "In vivo" plasma glucose fractional coefficient disappearance rate was lower (p less than 0.001) in H: 1.01 x 10(-2) +/- 0.09 x 10(-2) vs 2.61 x 10(-2) +/- 0.14 x 10(-2) in C, in spite of H showing hyperinsulin secretion. Hyperinsulinism was further documented by "in vitro" Iri release studies from incubated pancreas pieces. In the absence of glucose (G) from the incubation medium H produced 541 +/- 19.8 mU/mg weight Tissue/20', while C produced 91.2 +/- 12.7 (p less than 0.001). With 100 mg% G, H released 1058 +/- 259 and C 377 +/- 82.5 (p less than 0.001). It is suggested that hyperinsulin secretion plus insulin resistance may account for the above findings.     

Effect of substance P on cardiovascular and respiratory function in subjects

The effect of substance P (SP), administered both intravenously and by inhalation, has been studied in normal and asthmatic humans. Intravenous infusion of SP (0.2-3.3 pmol X kg-1 X min-1) achieving a plasma concentration of SP between 5 and 25 pM produced vasodilatation (mean +/- SD), maximal increase in skin temperature (0.9 +/- 0.3 degree C) (P less than 0.05), and fall in diastolic blood pressure (8.5 +/- 2.9 mmHg) (P less than 0.05) associated with an increase in heart rate (15 +/- 10 beats/min) (P less than 0.05). All subjects had a fall in Vp30 (airflow at 70% of forced vital capacity measured from total lung capacity after a forced partial expiratory flow maneuver) at low infusion rate (P less than 0.05) and a significant rise at the highest infusion rate (P less than 0.05). Ventilation at rest and when stimulated by transient hypoxia increased (mean increase in resting ventilation 0.73 +/- 0.4 l/min and mean percent increase in transient ventilatory hypoxic response 41 +/- 27%). There was a small nonsignificant increase in plasma norepinephrine but no change in epinephrine or histamine. Inhaled SP, up to 0.7 mumol, caused a small nonsignificant fall in airway function in asthmatic subjects. SP has demonstrable effects on vascular smooth muscle and control of ventilation but at the doses studied had little effect on airway function.     

Exercise capacity, energy metabolism, and beta-adrenoceptor blockade. Comparison between a beta 1-selective and a non-selective beta blocker

The effects of beta 1 and beta 1/2 blockade on exercise capacity were studied in 9 healthy normotensive subjects. Progressive maximal bicycle ergometer tests, followed by an endurance test at 80% of maximal work load, were performed during randomized, double-blind 3 day treatment periods with placebo, atenolol (beta 1) and oxprenolol (beta 1/2). The reduction of maximal work capacity (ca. 10%) was similar with atenolol and oxprenolol, despite a more pronounced maximal heart rate reduction with atenolol (from 175 +/- 2 to 132 +/- 3 beats.min-1) than with oxprenolol (to 138 +/- 2 beats.min-1). Exercise time during the endurance test was reduced from 36 +/- 4 min with placebo to 27 +/- 3 min with atenolol (p less than 0.05) and 24 +/- 3 min with oxprenolol (p less than 0.01) (atenolol vs. oxprenolol: p less than 0.05). During the endurance test, plasma glycerol and non-esterified fatty acid concentrations were reduced with both atenolol and oxprenolol. The glycerol reduction was more pronounced with oxprenolol than with atenolol, plasma NEFA concentrations being similar. Plasma glucose and lactate concentrations were reduced by oxprenolol but not with atenolol. These data show that submaximal exercise capacity at work loads representing similar relative exercise intensities is reduced during non-selective and beta 1-selective beta blockade. This reduction may be related to the effects of beta 1 blockade on energy metabolism, with possibly an additional effect of beta 2 blockade.     

Reversal of fatigue during prolonged exercise by carbohydrate infusion or ingestion

Seven cyclists exercised at 70% of maximal O2 uptake (VO2max) until fatigue (170 +/- 9 min) on three occasions, 1 wk apart. During these trials, plasma glucose declined from 5.0 +/- 0.1 to 3.1 +/- 0.1 mM (P less than 0.001) and respiratory exchange ratio (R) fell from 0.87 +/- 0.01 to 0.81 +/- 0.01 (P less than 0.001). After resting 20 min the subjects attempted to continue exercise either 1) after ingesting a placebo, 2) after ingesting glucose polymers (3 g/kg), or 3) when glucose was infused intravenously ("euglycemic clamp"). Placebo ingestion did not restore euglycemia or R. Plasma glucose increased (P less than 0.001) initially to approximately 5 mM and R rose (P less than 0.001) to approximately 0.83 with glucose infusion or carbohydrate ingestion. Plasma glucose and R then fell gradually to 3.9 +/- 0.3 mM and 0.81 +/- 0.01, respectively, after carbohydrate ingestion but were maintained at 5.1 +/- 0.1 mM and 0.83 +/- 0.01, respectively, by glucose infusion. Time to fatigue during this second exercise bout was significantly longer during the carbohydrate ingestion (26 +/- 4 min; P less than 0.05) or glucose infusion (43 +/- 5 min; P less than 0.01) trials compared with the placebo trial (10 +/- 1 min). Plasma insulin (approximately 10 microU/ml) and vastus lateralis muscle glycogen (approximately 40 mmol glucosyl U/kg) did not change during glucose infusion, with three-fourths of total carbohydrate oxidation during the second exercise bout accounted for by the euglycemic glucose infusion rate (1.13 +/- 0.08 g/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for estrogen-dependent blastocyst formation in the pig

The physiological significance of estradiol-17beta for the early embryonic development in the pig was investigated in vitro by four different experimental designs. A total of 1635 morphologically intact morulae were cultured in vitro in Krebs-Ringer bicarbonate solution supplemented with 10% heat-inactivated lamb serum, and the blastocyst formation rate (BFR) was recorded after 24 or 48 h. The addition of estradiol-17 beta (0.1 nM, 1 nM, 100 nM), progesterone (100 nM, 500 nM) or cortisol (100 nM) to the culture medium did not affect BFR (95 to 100%, Experiment 1). Similarly, adding charcoal-stripped lamb serum to the medium instead of normal lamb serum in the absence or presence of 1 nM estradiol-17 beta had no effect (93 to 95% BFR, Experiment 2). The antiestrogen Nafoxidine, however, at a concentration of 15 micrograms/ml, significantly (p less than 0.01) reduced BFR to 13.3 +/- 5.8% compared to controls (93.3 +/- 4.2%, Experiment 3). Supplementation with estradiol-17 beta (1 nM) in the presence of 15 micrograms/ml Nafoxidine significantly (p less than 0.01) improved BFR to 57.2 +/- 8.9%. Higher concentrations of estradiol-17 beta (100 nM, 100 microM) did not further enhance BFR. The stimulatory effects of estradiol-17 beta were specific since the BFR remained low in the presence of 100 nM progesterone (10.0 +/- 4.5%) or 100 nM cortisol (3.3 +/- 3.3%). Addition of 5% estradiol-17 beta-antiserum to the culture medium (Experiment 4) significantly (p less than 0.01) reduced BRF to 51.9 +/- 6.7% compared to controls (93.1 +/- 2.2%).(ABSTRACT TRUNCATED AT 250 WORDS)     

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).     

Role of endometrial blood flow assessment with color Doppler energy in predicting pregnancy outcome of IVF-ET cycles

This is a prospective study of 182 women (38 yrs or younger) undergoing IVF-ET. Endometrial thickness, echo pattern and blood flow on transvaginal ultrasonography were recorded eight hours prior to hCG administration. The patients were divided into three groups: A (n = 10) with undetectable endometrial blood flow; B (n = 82) with sub-endometrial blood flow; C (n = 90) with both endometrial and sub-endometrial blood flow. According to IVF-ET outcomes, all patients were re-divided into three groups: 1 non-pregnancy (n = 92); 2 intrauterine pregnancy with live fetus (n = 70); 3 others (n = 20 including biochemical pregnancy, embryonic diapause, ectopic pregnancy and miscarriage). Intrauterine pregnancy with live fetus in Group C (62.2%) was much higher than that in Group A and B (0% and 17.1%, p less than or equal to 0.001). The implantation rate (33.2%) was much higher than that in Group A and B (0% and 19.90%, p less than or equal to 0.001). The pulsatility index, resistance index, and S/D of endometrial spiral arteries were 0.1 +/- 0.2, 0.6 +/- 0.1 and 2.5 +/- 0.4 in Group 2, which were much lower than those in Group 1 and Group 3 (p1-2 less than 0.001, p2-3 less than 0.05). The patients with detectable endometrial blood flow had higher clinical pregnancy rates and implantation rates.     

Evidence of sustained forearm vasodilatation after brief isocapnic hypoxia.

Healthy subjects exposed to 20 min of hypoxia increase ventilation and muscle sympathetic nerve activity (MSNA). After return to normoxia, although ventilation returns to baseline, MSNA remains elevated for up to an hour. Because forearm vascular resistance is not elevated after hypoxic exposure, we speculated that the increased MSNA might be a compensatory response to sustained release of endogenous vasodilators. We studied the effect of isocapnic hypoxia (mean arterial oxygen saturation 81.6 +/- 4.1%, end-tidal Pco2 44.7 +/- 6.3 Torr) on plethysmographic forearm blood flow (FBF) in eight healthy volunteers while infusing intra-arterial phentolamine to block local alpha-receptors. The dominant arm served as control. Forearm arterial vascular resistance (FVR) was calculated as the mean arterial pressure (MAP)-to-FBF ratio. MAP, heart rate (HR), and FVR were reported at 5-min intervals at baseline, then while infusing phentolamine during room air, isocapnic hypoxia, and recovery. Despite increases in HR during hypoxia, there was no change in MAP throughout the study. By design, FVR decreased during phentolamine infusion. Hypoxia further decreased FVR in both forearms. With continued phentolamine infusion, FVR after termination of the exposure (17.47 +/- 6.3 mmHg x min x ml(-1) x 100 ml of tissue) remained lower than preexposure baseline value (23.05 +/- 8.51 mmHg x min x ml(-1) x 100 ml of tissue; P < 0.05). We conclude that, unmasked by phentolamine, the vasodilation occurring during hypoxia persists for at least 30 min after the stimulus. This vasodilation may contribute to the sustained MSNA rise observed after hypoxia.