Chronotropic and inotropic effects on the dog heart of stimulating the efferent cardiac sympathetic nerves

1. The chronotropic and inotropic responses of the dog heart to stimulation of the ansae subclaviae were studied.2. The maximum rate of rise of pressure in the left ventricle (dP/dt max) was used as an index of the inotropic changes.3. In experiments in which the secondary inotropic effects of changes in heart rate and blood pressure were prevented it was shown that, using stimuli which produced the same chronotropic response, stimulation of the left ansa subclavia resulted in an inotropic change which was about eight times greater than that which resulted from stimulation of the right ansa subclavia.4. In experiments in which heart rate and blood pressure were allowed to change freely it was shown that the secondary inotropic effects of changes in blood pressure and heart rate amounted to about 70% of the total inotropic change when the right ansa subclavia was stimulated and about 20% of the total change when the left ansa subclavia was stimulated.     

The effect of acute exercise with increasing workloads on inactive muscle blood flow and its heterogeneity in humans

The distribution of blood flow between active and inactive skeletal muscles has been sparsely studied in humans. Here we investigated non-exercising leg blood flow in six healthy young women during intermittent isometric one leg knee extension exercise with increasing workloads. Positron emission tomography was used to measure blood flow in hamstring muscles of the exercising leg, and whole thigh muscles as well as its knee extensor and hamstring compartment of the resting leg. Mean blood flow to the hamstrings of the exercising leg (5.8?±?2.6?ml/100?g/min during the highest exercise workload) and whole thigh muscle of the resting leg (7.1?±?3.8?ml/100?g/min) did not change significantly from rest (4.0?±?0.7 and 4.7?±?1.9?ml/100?g/min, respectively) to exercise, but flow heterogeneity increased substantially at increasing workloads. Importantly, during the highest exercise workload, mean blood flow in the knee extensors of the resting leg decreased (5.5?±?3.0?ml/100?g/min at rest and 3.4?±?2.0?ml/100?g/min during exercise, p?<?0.01) while flow heterogeneity increased (28?±?8% at rest and 83?±?26% during exercise, p?<?0.05). Conversely, in hamstring muscles of the resting leg blood flow increased from 3.9?±?1.0?ml/100?g/min at rest to 11.5?±?6.8?ml/100?g/min during exercise (p?<?0.05) while flow heterogeneity increased from 30?±?7 to 58?±?19% (p?<?0.05). In conclusion, while mean whole thigh muscle blood flow of the resting leg remains at resting level during one leg exercise of the contralateral leg, redistribution of blood flow between muscle parts occurs within the thigh. Based on previous studies, nervous constraints most probably act to cause this blood flow distribution.     

Middle cerebral artery blood velocity during exercise with β‐1 adrenergic and unilateral stellate ganglion blockade in humans

A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA V_mean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA V_mean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V_mean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA V_mean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s^?1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min^?1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min^?1) and ΔMCA V_mean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s^?1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA V_mean (10.2 ± 2.5 cm s^?1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system.     

Spatial heterogeneity of blood flow in the dog heart. I. Glucose uptake,free adenosine and oxidative/glycolytic enzyme activity

 The spatial heterogeneity of myocardial perfusion and metabolism was studied in 11 anaesthetized dogs under resting conditions. In each heart local myocardial blood flow was assessed using the tracer microsphere technique in 256 samples (mean mass: 83.1 mg) taken from the left anterior ventricular wall. In the same samples, the following biochemical parameters were determined: accumulation of [³H]-deoxyglucose (a measure of glucose uptake), free cytosolic adenosine (S-adenosylhomocysteine accumulation technique, a measure of tissue oxygenation and a possible mediator of blood flow regulation), and the specific activities of oxidative (citrate synthase, cytochrome-c-oxidase) and glycolytic (hexokinase, phosphoglycerate kinase) enzymes. Capillary density and mitochondrial and myofibril volume densities were determined by morphometry. Myocardial perfusion in each sample (average 0.77 ml min⁻¹ g⁻¹) varied between 0.1 and 2.5 times the mean (coefficient of variation 0.30±0.02). [³H]-deoxyglucose was deposited locally in proportion to perfusion. Samples showing low flow (<0.2 ml min⁻¹ g⁻¹) did not exhibit increased levels of cytosolic adenosine. The specific activities of the oxidative and glycolytic enzymes, however, were uniformly distributed between low and high flow areas. Furthermore, capillary density and mitochondrial and myofibril densities were similar in high and low flow regions. The results show firstly that local glucose metabolism in the heart occurs in proportion to local blood flow, suggesting that high flow regions have a higher than average metabolic rate. Secondly, regions of low flow are not compromized by critical oxygenation and most likely have a lower than average oxygen demand and finally, the homogeneous distribution of oxidative and glycolytic enzymes, as well as the homogeneous myocardial ultrastructure, suggest that areas with high and low blood flow under resting conditions may increase their metabolic rate to similar levels when required. Received: 19 January 1996 / Received after revision and accepted: 31 March 1996     

Heart and brain circulation and CO2 in healthy men

Aim: To compare blood flow response to arterial carbon dioxide tension change in the heart and brain of normal elderly men. Methods: Thirteen healthy elderly male volunteers were studied. Hypercapnea was induced by carbon dioxide inhalation and hypocapnea was induced by hyperventilation. Myocardial blood flow [mL min^?1 × (100 g of perfusable tissue)^?1] and cerebral blood flow [mL min^?1 × (100 g of perfusable tissue)^?1] were measured simultaneously at rest, under carbon dioxide gas inhalation and hyperventilation using the combination of two positron emission tomography scanners. Results: Arterial carbon dioxide tension increased significantly during carbon dioxide inhalation (43.1 ± 2.7 mmHg, P < 0.05) and decreased significantly during hyperventilation (29.2 ± 3.4 mmHg, P < 0.01) from baseline (40.2 ± 2.4 mmHg). Myocardial blood flow increased significantly during hypercapnea (88.7 ± 22.4, P < 0.01) from baseline (78.2 ± 12.6), as did the cerebral blood flow (baseline: 39.8 ± 5.3 vs. hypercapnea: 48.4 ± 10.4, P < 0.05). During hypocapnea cerebral blood flow decreased significantly (27.0 ± 6.3, P < 0.01) from baseline as did the myocardial blood flow (55.1 ± 14.6, P < 0.01). However, normalized myocardial blood flow by cardiac workload [100 mL mmHg^?1 × (heart beat)^?1 × (gram of perfusable tissue)^?1] was not changed from baseline (93.4 ± 16.6) during hypercapnea (90.5 ± 14.3) but decreased significantly from baseline during hypocapnea (64.5 ± 18.3, P < 0.01). Conclusion: In normal elderly men, hypocapnea produces similar vasoconstriction both in the heart and brain. Mild hypercapnea increased cerebral blood flow but did not have an additional effect to dilate coronary arteries beyond the expected range in response to an increase in cardiac workload.     

High afterload during 10 min of regional ischaemia affects diastolic creep but not systolic function in reperfused (stunned) myocardium

The effect of afterload during regional ischaemia on myocardial stunning was studied in 15 pentobarbital anaesthetized cats. 10 min occlusion of the left anterior descending artery (LAD) was followed by 60 min of reperfusion. Afterload was decreased by intravenous infusion of nitroglycerine 3–8 μg kg^-1 min^-1 in group I (n=8); left ventricular peak systolic pressure (LVSP) 84±4 mmHg (mean±SEM) during coronary artery occlusion. In group II (n=7) LVSP was increased to 188±10 mmHg by inflating an intraaortic balloon during coronary artery occlusion. Regional function in the LAD perfused region was evaluated by cross-oriented sonomicrometry. Myocardial tissue blood flow was evaluated by radio-labelled microspheres. Afterload alterations did not affect regional systolic shortening (10.8±2.0% vs. 11.0±1.5% in group I and II, respectively, after 60 min of reperfusion). However, increased end-diastolic dimensions (diastolic creep) in both the circumferential and longitudinal segments were markedly more pronounced in the high afterload group (group II). Also important, the markedly increased myocardial tissue blood flow during reperfusion in group II as compared with group I (2.30±0.18 vs.  1.34±0.08 mL min^-1 g^-1 and 2.58±0.23 vs. 1.49±0.07 mL min^-1 g^-1 in subepicardial and subendocardial layers in the LAD perfused region) suggests that increased diastolic creep increased metabolic demands. This study indicates that passive stretching of the ischaemic area during coronary artery occlusion is an important mechanism behind diastolic creep.     

Blood flow in the rabbit tenuissimus muscle Influence of preparative procedures for intravital microscopic observation

LINDBOM, L., TUMA, R. F. & ARFORS, K.-E.: Blood flow in the rabbit tenuissimus muscle: Influence of preparative procedures for intravital microscopic observation. Acta Physiol Scand 1982, 114 :121–127. Received 21 April 1981. ISSN 0001–6772. Department of Experimental Medicine, Pharmacia AB, Uppsala, Sweden. The tenuissimus muscle in the rabbit and the cat is a suitable tissue for intravital microscopic investigation of skeletal muscle blood flow. In this study the influence of surgical procedures necessary for direct microscopic observation on the physiological state of the rabbit tenuissimus muscle was assessed by means of blood flow measurements. Mean resting blood flow was 2.8±0.8 (mean ± S.D.) ml. min^-1. 100 g^-1 in the left tenuissimus muscle when prepared for microscopic observation as determined by the radioactive microsphere method. This value was not significantly different from that in the intact unexposed muscle in the contralateral leg, 3.3 ±1.1 ml. min^-1. 100 g^-1. Exposure of the muscle to atmospheric oxygen tension resulted in a reduction of blood flow to 0.7±0.4 ml. min^-l. 100g^-l, suggesting that local metabolic control mechanisms were active. The normal range of vascular control seemed to be maintained, as demonstrated by an increase in blood flow to 64.2± 18.8 ml. min-¹. 100 g^-l during “maximal” vasodilation induced by topical application of PGE₁. The tenuissimus muscle showed a marked sensitivity to mechanical stimulation. Slight stretching of the muscle, similar to what may occur during surgical preparation, resulted in an increase in blood flow to 17.5±5.7 ml. min^-1. 100 g^-1. Flow values calculated from data obtained by direct microscopic measurements in the tenuissimus muscle agreed well with those obtained by the microsphere method.     

Adaptations of aortic and pulmonary artery flow parameters measured by phase-contrast magnetic resonance angiography during supine aerobic exercise

Purpose

Increased oxygen uptake and utilisation during exercise depend on adequate adaptations of systemic and pulmonary vasculature. Recent advances in magnetic resonance imaging techniques allow for direct quantification of aortic and pulmonary blood flow using phase-contrast magnetic resonance angiography (PCMRA). This pilot study tested quantification of aortic and pulmonary haemodynamic adaptations to moderate aerobic supine leg exercise using PCMRA.

Methods

Nine adult healthy volunteers underwent pulse gated free breathing PCMRA while performing heart rate targeted aerobic lower limb exercise. Flow was assessed in mid ascending and mid descending thoracic aorta (AO) and main pulmonary artery (MPA) during exercise at 180 % of individual resting heart rate. Flow sequence analysis was performed by experienced operators using commercial offline software (Argus, Siemens Medical Systems).

Results

Exercise related increase in HR (rest: 69 ± 10 b min^?1, exercise: 120 ± 13 b min^?1) resulted in cardiac output increase (from 6.5 ± 1.4 to 12.5 ± 1.8 L min^?1). At exercise, ascending aorta systolic peak velocity increased from 89 ± 14 to 122 ± 34 cm s^?1 (p = 0.016), descending thoracic aorta systolic peak velocity increased from 104 ± 14 to 144 ± 33 cm s^?1 (p = 0.004), MPA systolic peak velocity from 86 ± 18 to 140 ± 48 cm s^?1 (p = 0.007), ascending aorta systolic peak flow rate from 415 ± 83 to 550 ± 135 mL s^?1 (p = 0.002), descending thoracic aorta systolic peak flow rate from 264 ± 70 to 351 ± 82 mL s^?1 (p = 0.004) and MPA systolic peak flow rate from 410 ± 80 to 577 ± 180 mL s^?1 (p = 0.006).

Conclusion

Quantitative blood flow and velocity analysis during exercise using PCMRA is feasible and detected a steep exercise flow and velocity increase in the aorta and MPA. Exercise PCMRA can serve as a research and clinical tool to help quantify exercise blood flow adaptations in health and disease and investigate patho-physiological mechanisms in cardio-pulmonary disease.     

Minimal effects of nitric oxide on spatial blood flow heterogeneity of the dog heart

 Eleven Beagle dogs were studied to elucidate the possible role of L-arginine-derived nitric oxide on local blood flow distribution in left and right ventricular myocardium. Local blood flow was determined in 256 samples from the left and 64 samples from the right ventricle per heart using the tracer microsphere technique (mean sample mass 319 ± 131 mg). Nitric oxide production was effectively inhibited by intravenous infusion of 20 mg/kg nitro-L-arginine methylester (L-NAME) as evidenced by a shift of the dose/response curve for the effect of intracoronary administration of bradykinin (0.004–4.0 nmol/min) on coronary blood flow. L-NAME enhanced left and right ventricular systolic pressures from 132 ± 18 to 155 ± 15 mm Hg and from 26 ± 3 to 29 ± 3 mm Hg respectively (both P = 0.043). Mean left ventricular blood flow was 1.14 ± 0.38 before and 0.99 ± 0.28 ml min^–1 g^–1 after L-NAME (P = 0.068), while right ventricular blood flow fell from 0.72 ± 0.28 to 0.53 ± 0.20 ml min^–1 g^–1 (P = 0.043). Coronary conductance of left and right ventricular myocardium fell by 31 and 43% respectively (both P = 0.043). The coefficient of variation of left ventricular blood flow was 0.26 ± 0.07 before and 0.29 ± 0.07 after L-NAME (P = 0.068), that of right ventricular blood flow was 0.27 before and after L-NAME. Skewness (0.51) and kurtosis (4.23) of left ventricular blood flow distribution were unchanged after L-NAME, while in the right ventricle skewness decreased from 0.54 to 0.09 (P = 0.043) and kurtosis (3.68) tended to decrease after L-NAME (P = 0.080). The fractal dimension (D = 1.20–1.27) and the corresponding nearest-neighbor correlation coefficient (r _n = 0.37–0.53) of left and right ventricular myocardium remained unchanged after infusion of L-NAME. From these results it is concluded that firstly, local nitric oxide release does not explain the higher perfusion of physiological high flow samples and secondly, that spatial myocardial blood flow coordination is not dependent on nitric oxide. Received: 11 July 1996 / Received after revision: 29 October 1996 / Accepted: 17 December 1996     

Normovolaemic haemodilution and hyperoxia have no effect on fractal dimension of regional myocardial perfusion in dogs

Hypervolaemic haemodilution makes myocardial perfusion more homogenous as reflected by reduced fractal dimension of regional myocardial perfusion. The clinically more commonly performed acute normovolaemic haemodilution, however, has not yet been studied in this respect. Hyperoxic ventilation with 100% oxygen is used in conjunction with haemodilution to compensate for low oxygen content by increasing physically dissolved oxygen in plasma. Since hyperoxia is known to cause disturbance in microcirculatory regulation we studied the effects of acute normovolaemic haemodilution to haematocrit (hct) 20 ± 1% and hyperoxia on regional myocardial perfusion heterogeneity in 22 anaesthetized dogs using fractal and correlation analysis. Regional myocardial perfusion was assessed with radioactive microspheres. The results of the study were that heart rate, blood volume and arterial pressure were unchanged during haemodilution. Cardiac index was 3.6 ± 0.7 L min^?1 m^?2 before and 4.6 ± 0.7 L min^?1 m^?2 after haemodilution (P < 0.05). Fractal dimension (D) of regional myocardial perfusion was 1.17 ± 0.10 at baseline. Neither haemodilution (D = 1.19 ± 0.10) nor hyperoxia (D = 1.17 ± 0.10) altered fractal properties of regional myocardial perfusion. Spatial correlation of blood flow to adjacent tissue samples before haemodilution was 0.58 ± 0.15. Haemodilution and hyperoxia did not significantly influence spatial correlation (0.57 ± 0.12 vs. 0.60 ± 0.09; ns). We conclude that neither acute normovolaemic haemodilution nor haemodilution in combination with hyperoxic ventilation alter physiological myocardial perfusion heterogeneity.     

Central and peripheral cardiovascular adaptations to exercise in endurance‐trained children

Stroke volume (SV) response to exercise depends on changes in cardiac filling, intrinsic myocardial contractility and left ventricular afterload. The aim of the present study was to identify whether these variables are influenced by endurance training in pre‐pubertal children during a maximal cycle test. SV, cardiac output (Doppler echocardiography), left ventricular dimensions (time–movement echocardiography) as well as arterial pressure and systemic vascular resistances were assessed in 10 child cyclists (VO_2max: 58.5 ± 4.4 mL min^?1 kg^?1) and 13 untrained children (UTC) (VO_2max: 45.9 ± 6.7 mL min^?1 kg^?1). All variables were measured at the end of the resting period, during the final minute of each workload and during the last minute of the progressive maximal aerobic test. At rest and during exercise, stroke index was significantly higher in the child cyclists than in UTC. However, the SV patterns were strictly similar for both groups. Moreover, the patterns of diastolic and systolic left ventricular dimensions, and the pattern of systemic vascular resistance of the child cyclists mimicked those of the UTC. SV patterns, as well as their underlying mechanisms, were not altered by endurance training in children. This result implied that the higher maximal SV obtained in child cyclists depended on factors influencing resting SV, such as cardiac hypertrophy, augmented myocardium relaxation properties or expanded blood volume.     

Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass

We tested the hypothesis that pharmacological reduction of the increase in cardiac output during dynamic exercise with a large muscle mass would influence the cerebral blood velocity/perfusion. We studied the relationship between changes in cerebral blood velocity (transcranial Doppler), rectus femoris blood oxygenation (near-infrared spectroscopy) and systemic blood flow (cardiac output from model flow analysis of the arterial pressure wave) as induced by dynamic exercise of large (cycling) vs. small muscle groups (rhythmic handgrip) before and after cardioselective β₁ adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.). During rhythmic handgrip, the increments in systemic haemodynamic variables as in middle cerebral artery mean blood velocity were not influenced significantly by metoprolol. In contrast, during cycling (e.g. 113 W), metoprolol reduced the increase in cardiac output (222 ± 13 vs. 260 ± 16%), heart rate (114 ± 3 vs. 135 ± 7 beats min^?1) and mean arterial pressure (103 ± 3 vs.112 ± 4 mmHg), and the increase in cerebral artery mean blood velocity also became lower (from 59 ± 3 to 66 ± 3 vs. 60 ± 2 to 72 ± 3 cm s^?1; P < 0.05). Likewise, during cycling with metoprolol, oxyhaemoglobin in the rectus femoris muscle became reduced (compared to rest; ?4.8 ± 1.8 vs. 1.2 ± 1.7 μmol L^?1, P < 0.05). Neither during rhythmic handgrip nor during cycling was the arterial carbon dioxide tension affected significantly by metoprolol. The results suggest that as for the muscle blood flow, the cerebral circulation is also affected by a reduced cardiac output during exercise with a large muscle mass.     

Cardiac cyclic nucleotides and norepinephrine during neural sympathetic stimulation

The role of the cardiac cyclic nucleotides, adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP), and norepinephrine (NE) in cardiac responses to stimulation of the left ansa subclavia were studied in anesthetized open-chest dogs. In three groups of dogs undergoing stimulation for 6 min with impulse frequencies of 4, 10, or 20 Hz and 5 V, left ventricular levels of cAMP, cGMP, and NE were determined at the end of the stimulation period and compared to control dogs. A significant elevation in cAMP (avg 67%) was found at all three frequencies. Myocardial NE decreased by an average of 58% from control by the end of the stimulation period, regardless of the stimulation frequency. The rate of left ventricular pressure rise (LV dP/dt) was found to be linearly related to the increase in myocardial cAMP (P less than 0.01) rather than to NE levels found after stimulation. Propranolol administered before ansa subclavia stimulation caused significant decreases in both cAMP and LV dP/dt, whereas the muscarinic agonist carbachol, caused increases in cGMP and NE and a decrease in LV dP/dt accompanied by a nonsignificant decline in cAMP. The elevation in levels of cGMP and NE and the decrease in LV dP/dt to carbachol were blocked with atropine. Results from pretreating dogs with propranolol and carbachol followed by neural sympathetic stimulation indicated the importance of beta-adrenergic and muscarinic receptors in modifying cardiac function through the production of the cyclic nucleotides. Sustained cardiac responses during ansa subclavia stimulation at physiological levels could be related to the accelerated synthesis of endogenous cAMP.     

Influence of adenosine on the vascular responses to sympathetic nerve stimulation in the canine subcutaneous adipose tissue

Adenosine appears to regulate resting blood flow in canine subcutaneous adipose tissue. Sympathetic nerve stimulation has been shown to enhance the adenosine production in this tissue. This study therefore tested the possibility that adenosine may influence the vascular responses to sympathetic nerve stimulation. Intraarterial infusion of adenosine (5–20 μM in arterial blood) increased the resting vascular conductance (from 0.048 ± 0.007 to 0.095 ± 0.013 ml ± min^-1100 g^-1± mmHg^-1) and the percental reduction in vascular conductance due to sympathetic nerve stimulation (4 Hz) by 34 per cent (p<0.05) and to i. a.noradrenaline by 27 per cent (p<0.05). The vasodilator response due to nerve stimulation after α-blockade was reduced by adenosine. Dipyridamole (0.5–1.5 μM) + EHNA (3–10 μM), which increases plasma adenosine levels, had similar effects to adenosine, while theophylline (30–80 μM) decreased the vasoconstrictor response. The vasoconstrictor escape was enhanced by EHNA alone and in combination with dipyridamole, but was reduced by theophylline. On the other hand, the poststimulatory hyperemia was unaffected by adenosine, dipyridamole and EHNA, and theophylline. The results show that adenosine does not reduce the magnitude of the initial vasoconstrictor response in proportion to the increase in resting blood flow. The autoregulatory escape in adipose tissue during nerve stimulation appears to be mediated both by adenosine and by noradrenaline acting on β-adrenoceptors. Poststimulatory hyperemia does not seem to be greatly influenced by exogenous or endogenous adenosine     

Acute hyperglycaemia does not alter nitric oxide-mediated microvascular function in the skin of adolescents with type 1 diabetes

Purpose

We assessed the impact of an acute bout of hyperglycaemia on nitric oxide (NO)-mediated microvascular function in the skin of adolescents with type 1 diabetes (T1DM).

Methods

Twelve subjects (12–18 years) with T1DM were randomised into a control (n = 6) or hyperglycaemia (n = 6) group. Hyperinsulinaemic clamps were used to manipulate blood glucose level (BGL). Following a baseline period, where all subjects were euglycaemic (20 min), the experimental phase began. During the experimental phase, BGL was elevated to 16.7 ± 0.9 mmol L^?1 in the hyperglyceamic group, while it was maintained at euglycaemia (5.5 ± 0.1 mmol L^?1) in the control group. Simultaneously, cutaneous microvascular function (% max cutaneous vascular conductance, CVC%) was assessed using laser Doppler fluxometry following stimulation of skin blood flow using localised heating (42 °C). To determine the NO contribution to skin blood flow, two microdialysis sites were assessed, one perfused with Ringers and the other with the NO blocker, NG-monomethyl-l-arginine (l-NMMA).

Results

In the hyperglycaemic group, acute increase in BGL was not associated with changes in skin blood flow (CVC% 82.4 ± 8.7 % at 5.5 ± 0.1 mmol L^?1 vs 79.5 ± 9.1 % at 16.7 ± 0.9 mmol L^?1, unpaired t tests, P = 0.588) or the contribution of NO to vasodilation.

Conclusions

These results suggest that, in our group of adolescents with type 1 diabetes, acute hyperglycaemia did not affect skin microvascular NO-mediated function.     

K+ as a vasodilator in resting human muscle: implications for exercise hyperaemia

Aim: Potassium (K⁺) released from contracting skeletal muscle is considered a vasodilatory agent. This concept is mainly based on experiments infusing non‐physiological doses of K⁺. The aim of the present study was to investigate the role of K⁺ in blood flow regulation. Methods: We measured leg blood flow (LBF) and arterio‐venous (A‐V) O₂ difference in 13 subjects while infusing K⁺ into the femoral artery at a rate of 0.2, 0.4, 0.6 and 0.8 mmol min^?1. Results: The lowest dose increased the calculated femoral artery plasma K⁺ concentration by approx.1 mmol L^?1. Graded K⁺ infusions increased LBF from 0.39 ± 0.06 to 0.56 ± 0.13, 0.58 ± 0.17, 0.61 ± 0.11 and 0.71 ± 0.17 L min^?1, respectively, whereas the leg A‐V O₂ difference decreased from 74 ± 9 to 60 ± 12, 52 ± 11, 53 ± 9 and 45 ± 7 mL L^?1, respectively (P < 0.05). Mean arterial pressure was unchanged, indicating that the increase in LBF was associated with vasodilatation. The effect of K⁺ was totally inhibited by infusion (27 μmol min^?1) of Ba²⁺, an inhibitor of Kir2.1 channels. Simultaneous infusion of ATP and K⁺ evoked an increase in LBF equalled to the sum of their effects. Conclusions: Physiological infusions of K⁺ induce significant increases in resting LBF, which are completely blunted by inhibition of the Kir2.1 channels. The present findings in resting skeletal muscle suggest that K⁺ released from contracting muscle might be involved in exercise hyperaemia. However, the magnitude of increase in LBF observed with K⁺ infusion suggests that K⁺ only accounts for a limited fraction of the hyperaemic response to exercise.     

Fatty acids are important for the Frank–Starling mechanism and Gregg effect but not for catecholamine response in isolated rat hearts

In some pathophysiological conditions myocardial metabolism can switch from mainly long chain fatty acid (LCFA) oxidation to mainly glucose oxidation. Whether the predominant fatty acid or glucose oxidation affects cardiac performance has not been defined. In a buffer perfused isovolumetrically contracting rat heart, oxidation of endogenous pool LCFA was avoided by inhibiting carnitine‐palmitoyl‐transferase I (CPT‐I) with oxfenicine (2 mm ). In order to restore fatty acid oxidation, hexanoate (1 mm ), which bypasses CPT‐I inhibition, was added to the perfusate. Three groups of hearts were subjected to either an increase in left ventricular volume (VV, +25%) or an increase in coronary flow (CF, +50%), or inotropic stimulation with isoproterenol (10^?8 and 10^?6 m ). The increase in VV (the Frank–Starling mechanism) increased rate–pressure product (RPP) by 21 ± 2% under control conditions, but only by 6 ± 2% during oxfenicine‐induced CPT‐I inhibition. The contractile response to changes in VV recovered after the addition of hexanoate. Similar results were obtained in hearts, in which an increase in CF was elicited (the Gregg phenomenon). Isoproterenol caused a similar increase in contractility regardless of the presence of oxfenicine or hexanoate. In all groups, a commensurate increase in oxygen consumption accompanied the increase in contractility. The fatty acid oxidation is necessary for an adequate contractile response of the isolated heart to increased pre‐load or flow, whereas the inotropic response to adrenergic β‐receptor stimulation is insensitive to changes in substrate availability.     

Interrelatinoship between alpha- and beta-adrenergic agonists and histamine in canine airways

To determine the interrelationship between adrenergic receptors in airway smooth muscle and histamine-induced airway constriction, we studied the responses of 26 parasympathectomized dogs to selective and mixed alpha- and beta-adrenergic stimulation in situ by means of an isometric tracheal smoth-muscle preparation. Intra-arterial (IA) phenylephrine (PE) caused dose-related tracheal contraction beginning at 10^?8 mol; maximal active tension was 9.47 ± 2.2 gm F/cm (mean ± SD) at 10^?5 mol. Pretreatment with propranolol augmented tracheal contraction to PE (maximum 35.5 ± 3.2 gm F/cm). The contractile resposne to PE was blocked with a dose of phentolamine (200 μg/kg IA), which did not alter the respionse to acetylcholine. Isoproterenol (ISO) caused dose-related tarcheal relaxation beginning at 4.2 × 10^?11 mol (maximum 43.2 ± 19.6 gm F/cm). Norepinephrine (NE) also caused tracheal relaxation beginning at 1.2 × 10^?6 mol, which was less than relaxation caused by ISO. Prestimulation with histamine did not augment the contractile response to PE but reduced maximal tracheal relaxation to NE (p < 0.001). It is concluded that selective alpha-adrenergic stimulation causes tracheal contraction. However, nonselective stimulation results in tracheal relaxation, even with a weak beat-agonist such as NE. Histamine does not augment alpha-adrenergic contraction as previously suggested but causes physiologic antagonism of beta-adrenergic relaxation of tracheal muscle.     

Effects of endurance training on left ventricular performance: a study in anaesthetized rabbits

Endurance training is known to increase ventricular performance during exercise and to decrease resting heart rate. The aim of this study was to evaluate a model for endurance training in rabbits and to study the effects of endurance training on local myocardial performance in the left ventricle during resting conditions. One group of rabbits underwent a 10-week exercise training programme. The rabbits trained 5 days a week on a treadmill. Training periods increased gradually from 15 min to 1 h with increments in speed from 0.5 to 1.2 km h¹. After the training programme the rabbits were anaesthetized and studied as acute open-chest preparations. A micro-tip pressure transducer was introduced via apex to the left ventricle and two pairs of ultrasonic crystals were implanted in the left anterior wall to measure segment lengths. One pair measured shortening in the circumferential direction whereas the other pair measured shortening in the longitudinal direction. Heart rate was lower in the trained group (n = 5), 172 + 9 beats min“‘ (mean±SEM), compared with 235 ± 19 beats min ’ in the control group (n = 8) (P < 0.02). Stroke volume, measured by radio-nuclidelabelled microspheres, was greater in the trained rabbits compared with controls (P < 0.03). Shortening in both segments was of similar magnitude for the trained and control groups. End-systolic pressure-length relations (ESPLR) obtained by occlusion of the descending aorta (balloon catheter) showed reduced slopes for longitudinal segments in the trained group compared with the control group (P < 0.05). We conclude that this endurance training programme in rabbits can be used to study myocardial effects of endurance training. Furthermore, the less steep slope of ESPLRs for the longitudinal segment in the trained animals might indicate a structural myocardial remodelling and increased contractile reserve that might be recruited during adrenergic stimulation in the trained group.     

Effects of indomethacin on regional blood flow in conscious rabbits—a microsphere study

In an attempt to reveal the importance of prostaglandins in the control of regional blood flow 20 mg/kg b.wt. indomethacin was given i.v. in conscious resting rabbits. Regional blood flow determinations were made before and 20 min after the injection using the labelled microsphere technique. The blood flow in the stomach wall was reduced by 0.75 ± 0.17 g·min^-1·g^-1 from a level of 1.64 ± 0.24 g·min^-1·g^-1. In jejunum the corresponding figures were 0.44 ± 0.12 and 1.26 ± 0.17 and in the brain 0.29 ± 0.10 and 1.24 ± 0.10. The blood flow in the liver via the hepatic artery increased by 0.20 ± 0.02 g·min^-1·g^-1 from a level of 0.13 ± 0.02 g·min^-1·g^-1. In the retina there was a reduction in blood flow by 2.75 ± 1.03 mg·min^-1 from a starting level of 15.1 ± 2.3 mg·min^-1. In a number of other tissues investigated there were no significant effects of the drug. The results suggest that under resting conditions prostaglandins play a role in the control of blood flow in the gastrointestinal tract, the brain and the retina—tissues which are likely to be rather active under such conditions.