Ascending pathways mediating somatoautonomic reflexes in exercising dogs

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

Blood pressure of sinoaortic-denervated dogs is not increased by cardiac denervation

Although blood pressure rises markedly after acute sinoaortic denervation, animals with chronic sinoaortic denervation have normal or only slightly elevated mean arterial pressures. The present study was performed to determine whether reflexes from cardiac receptors exert antihypertensive effects and thereby lower blood pressure in animals with chronic sinoaortic denervation. We made multiple measurements of blood pressures in dogs with chronic sinoaortic denervation before and after their hearts were denervated surgically. Mean arterial pressure after cardiac denervation (100.3 +/- 4.2 mm Hg) was not significantly different from the mean pressures recorded before cardiac denervation in these sinoaortic-denervated dogs (104.8 +/- 3.1 mm Hg). Also, mean heart rate after cardiac denervation (107.4 +/- 5.5 beats/min) did not differ significantly from the mean heart rate recorded before cardiac denervation (107.2 +/- 5.9 beats/min). Cardiac denervation did, however, appear to reduce the lability of both blood pressure and heart rate in sinoaortic-denervated dogs. We conclude that cardiac receptors are not responsible for maintaining arterial pressure within essentially normal limits in animals with chronic sinoaortic denervation.     

Respiratory muscle blood flow in exercising dogs after pneumonectomy.

In three foxhounds after left pneumonectomy, the relationships of ventilatory work and respiratory muscle (RM) blood flow to ventilation (VE) during steady-state exercise were examined. VE was measured using a specially constructed respiratory mask and a pneumotach; work of breathing was measured by the esophageal balloon technique. Blood flow to RM was measured by the radionuclide-labeled microsphere technique. Lung compliance after pneumonectomy was 55% of that before pneumonectomy; compliance of the thorax was unchanged. O2 uptake (VO2) of RM comprised only 5% of total body VO2 at exercise. At rest, inspiratory muscles received 62% and expiratory muscles 38% of the total O2 delivered to the RM (QO2RM). During exercise, inspiratory muscles received 59% and expiratory muscles 41% of total QO2RM. Blood flow per gram of muscle to the costal diaphragm was significantly higher than that to the crural diaphragm. The diaphragm, parasternals, and posterior cricoarytenoids were the most important inspiratory muscles, and internal intercostals and external obliques were the most important expiratory muscles for exercise. Up to a VE of 120 l/min through one lung, QO2RM constituted only a small fraction of total body VO2 during exercise and maximal vasodilation in the diaphragm was never approached.     

Alpha-adrenergic vasoconstrictor tone limits right coronary blood flow in exercising dogs

In exercising dogs, increased myocardial O2 consumption (MVO2) of the left ventricle is met primarily by hyperemia, whereas increased O2 extraction makes a greater contribution to right ventricular (RV) O2 supply. We hypothesized that alpha-adrenergic vasoconstrictor tone limits right coronary (RC) blood flow during exercise, forcing increased O2 extraction. This tone might also contribute to lesser RC vascular conductance at rest. Accordingly, RV O2 balance was examined at rest and during graded treadmill exercise before and during alpha-adrenergic blockade with phentolamine (1 mg/kg, i.v., n=6). The transmural distribution of RC flow was measured with radiolabeled microspheres in 4 additional dogs. At rest, alpha-adrenergic receptor blockade did not significantly increase RC flow or conductance. During exercise, alpha-adrenergic blockade increased RC flow and conductance responses to increased RV MVO2 by 25% and 60%, respectively. The transmural distribution of RC flow was not altered by exercise or by alpha-adrenergic blockade. Before alpha-adrenergic blockade, hyperemia provided 39%-66% of the additional O2 consumed by the right ventricle during graded exercise; after alpha-adrenergic blockade, hyperemia contributed 74%-85%. After alpha-adrenergic blockade, the slope of the relationship between RC venous PO2 and RV MVO2 became less steep, reflecting less O2 extraction due to enhanced hyperemia. Additional experiments were conducted on 5 anesthetized, open-chest dogs with constant RC perfusion pressure and beta-adrenergic blockade. The RC flow response to intracoronary norepinephrine was shifted to the left compared with that measured in the left coronary circulation, consistent with observations in the conscious exercising dogs. In conclusion, alpha-adrenergic vasoconstrictor tone does not restrict resting RC blood flow, but during exercise, this tone transmurally blunts RC hyperemia and forces the right ventricle to mobilize its O2 extraction reserve. This effect is more pronounced than has been reported for the left ventricle.     

Analysis of bronchovascular downstream blood pressure changes in exercising sheep

The relative roles of neural and pressure gradient factors, causing a fall or maintenance of bronchial blood flow in exercising sheep, are unknown. These were examined in sheep prepared under thiopentone/isoflurane general anaesthesia with a pulsed Doppler probe mounted on the bronchial artery, and aortic pressure (Pa) catheter in superficial cervical artery. After recovery, Swan-Ganz catheters were inserted under local anaesthesia into the pulmonary artery. Bronchial flow and conductance (Qbr, Cbr), and pressure gradients (Pg; i.e. aortic minus right atrial, Pg_RAP; pulmonary artery, Pg_Ppa; and, left atrial (wedge) Pg_LAP) were derived from continuous records, after switching between downstream sites during and after moderately severe treadmill exercise (3.8 km.h(-1), for 1.7 min, 6 min recovery). The protocol was repeated after combined alpha1,alpha2-adrenoceptor/cholinoceptor blockade using phentolamine methanesulfonate and methscopolamine bromide. Bronchial flow fell in both receptor intact (INT) and (BL) blocked state. Pa rose in INT, but downstream pressures rose only 3.7 (RAP), 2.8 (Ppa) and 2.0 (LAP) mmHg (P for each < 0.05) in both INT and BL. Pg_RAP and Pg_Ppa did not rise, but Pg_LAP rose 4.0 mmHg (P < 0.05). In BL, Pa fell, as did Pg_RAP (7.0 mmHg, P < 0.05), Pg_Ppa (8.9 mmHg, P < 0.001), but Pg_LAP did not change. Thus, downstream pressures change by small amounts, and pressure gradients to RAP and Ppa sites do not change during moderately severe exercise in normal sheep. The fall in Qbr in INT is due to neural factors, but in BL is due to a fall in Pg. The relative rise in Pg_LAP in both INT and BL favours redistribution within total Qbr to the pulmonary capillary/vein/left atrium site.     

Relationship between turnover rate and blood concentration of lactate in exercising dogs.

Steady-state blood lactate concentrationss and lactate turnover, or entry, rates were determined by use of constant infusion of L(+)-[14C]lactate in seven anesthetized dogs before and during electrically induced exercise. Lactate entry rates increased during exercise in all dogs with or without the infusion of additional exogenous cold lactate. Blood lactate concentrations, on the other hand, rose to levels considerably below those predicted for these entry rates in a previous study of the relationship in normal nonexercising dogs. It is concluded that improved efficiency of lactate removal during exercise allows low blood concentrations despite large increases in entry rates.     

Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs

Brändle, Marian, Kaushik P. Patel, Wei Wang, andIrving H. Zucker. Hemodynamic and norepinephrine responses topacing-induced heart failure in conscious sinoaortic-denervated dogs.J. Appl. Physiol. 81(4):1855-1862, 1996.The present study was undertaken to determinethe effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations thatoccur in the pacing-induced model of congestive heart failure. Twogroups of dogs were examined: intact(n = 9) and SAD(n = 9). Both groups of dogs werestudied in the control (prepace) state and each week after theinitiation of ventricular pacing at 250 beats/min. After the pacemakerwas turned off, hemodynamic and plasma norepinephrine levels returnedtoward control levels in the prepaced state and after 1 and 2 wk ofpacing. However, by 3 wk all hemodynamic and norepinephrine levelsremained relatively constant over the 10-min observation period withthe pacemaker off. With the pacemaker off, left ventricularend-diastolic pressure went from 2.7 ± 1.4 (SE) mmHg during theprepace state to 23.2 ± 2.9 mmHg in the heart failure state inintact dogs (P < 0.01). Leftventricular end-diastolic pressure increased to 27.1 ± 2.2 mmHgfrom a control level of 4.2 ± 1.9 mmHg in SAD dogs(P < 0.0003). Mean arterial pressuresignificantly decreased in intact and SAD dogs. Resting heart rate wassignificantly higher in SAD dogs and increased to 135.8 ± 8.9 beats/min in intact dogs and 136.1 ± 6.5 beats/min in SAD dogs.There were no significant differences in the hemodynamic parametersbetween intact and SAD dogs after pacing. Plasma norepinephrine wassignificantly lower in intact than in SAD dogs before pacing (197.7 ± 21.6 vs. 320.6 ± 26.6 pg/ml;P < 0.005). In the heart failurestate, plasma norepinephrine increased significantly in both intact(598.3 ± 44.2 pg/ml) and SAD (644.0 ± 64.6 pg/ml) groups. Therewere no differences in the severity or the magnitude of the developedheart failure state in SAD vs. intact dogs. We conclude from these datathat the arterial baroreflex is not the sole mechanism for the increasein sympathetic drive in heart failure.

     

Renal reflexes in the regulation of blood pressure and sodium excretion

The rich innervation of the kidney is distributed to all structures of renal parenchyma thus providing important anatomical support to the functional evidence that the renal nerves can control kidney functions and send signals on the kidney environment to the central nervous system. Efferent renal nerve fibres are known to influence renal haemodynamics by modifying arteriolar vascular tone, renin release by a direct action on juxtaglomerular cells, and the excretion of sodium and water by changing tubular reabsorption of sodium and water at the different tubular levels. Mechano- and chemo-receptors have been shown in the kidney. Afferent fibres connected with renal receptors convey signals to the central nervous system both at spinal and supraspinal levels. The central areas receiving inputs from the kidney are those involved in the control of cardiovascular homeostasis and fluid balance. Activation of renal receptors by the electrical stimulation of renal afferent fibres were found to elicit both excitatory and inhibitory sympathetic responses. Although the existence of excitatory renorenal reflexes has been suggested, electrophysiological and functional data demonstrate that neural renorenal reflexes exert a tonic inhibitory influence on the tubular sodium and water reabsorption and on the secretion of renin from the juxtaglomerular cells.