The Role of the Membrane Potential of Endothelial and Smooth Muscle Cells in the Regulation of Coronary Blood Flow

Membrane Potential of Coronary Endothelial and Smooth Muscle Cells. In the mammalian heart the supply of oxygen and energy-rich substrates through the coronary arterioles is continuously adapted to the variations of cardiac work. The coronary resistance arteries and the surrounding myocardium form a functional unit with multiple interactions between coronary endothelial cells, smooth muscle cells, perivascular nerves, and cardiac muscle cells. We describe the mechanisms underlying the electrical and chemical communication between the different cell types, the ionic channels contributing to the resting potential of endothelial and smooth muscle cells, and the mechanisms responsible for modulation of the resting potential. The main conclusion of our analysis is that the membrane potential of coronary endothelial and smooth muscle cells is one of the major determinants of coronary blood flow, and that modulation of the membrane potential provides a way to dilate or constrict coronary resistance arteries. It is proposed that the membrane potential of the myo-endothelial regulatory unit, i.e., of the endothelial cells and the underlying smooth muscle cells in the terminal arterioles, may function as an integrator of the numerous local and global vasodilator and constrictor signals that provide for the adaptation of coronary blood flow to the metabolic demands of the heart.     

Nocturnal temperature and subcutaneous blood flow in humans

Summary. The aim of this study was to investigate the possible relationship between variations in local skin and body temperatures, and a subcutaneous hyperaemia response during sleep in humans. Nocturnal subcutaneous blood flow (SBF) was measured in the lower legs of 9 subjects for 8–12 h under outpatient conditions. The core temperature was measured by a tympanic membrane temperature sensor, and the local skin temperature was measured by a skin temperature sensor. The ¹³³Xe wash-out technique with portable CdTe(Cl) detectors was used for measurement of the SBF. The SBF increased significantly (P<0.0001) after 1 h sleep, with the hyperaemia persisting for 2 h. During the hyperaemic phase, the local skin temperature increased significantly (P<0.0001) and then decreased again in the post-hyperaemic phase (P<0.01). The core temperature decreased significantly during the measurement period (P<0.01). Separate ordinary linear regression analyses revealed no significant correlations between the measured temperature parameters and the blood flow levels during sleep. The results indicate no governing role of the local skin or body temperatures on the local SBF. The local skin temperature increased significantly secondary to the nocturnal subcutaneous hyperaemia (i.e. active vasodilatation), which is believed to be involved in a thermoregulatory effector mechanism.     

Skin vasodilator response to local heating in human chronic spinal cord injury

Local heating evokes an increase in skin blood flow (SkBF), which consists of an initial peak (axon-reflex mediated) followed by a brief nadir and a secondary rise to a plateau. The aim of this study was to investigate whether heat provoked vasodilatation detects sympathetic vasomotor dysfunction and completeness of injury in patients with spinal cord injury (SCI). Twelve (seven complete, and five incomplete; level C4-L4) SCI patients, and nine healthy subjects as controls were studied. Thermostatic laser Doppler probes, which heat the skin locally, were placed on the dorsum of the hand and foot. SkBF was measured by laser Doppler flowmetry at baseline and at the first peak of vasodilatation (SkBF(max)). On the hand, SkBF at baseline and SkBF(max) were similar between the three groups. On the foot, SkBF at baseline was similar between the three groups but SkBF(max) was significantly diminished in complete SCI patients compared with controls (P < 0.01). In conclusion, heat provoked axon-reflex vasodilatation was diminished in the foot, below the level of lesion, in complete SCI. This test, that evaluates localized sympathetic vasomotor dysfunction, may be a useful non-invasive technique to detect completeness of autonomic disruption after SCI.     

Neurogenic forearm vasodilatation during contralateral isometric exercise is attenuated in diabetes mellitus

The responses in heart rate, blood pressure and blood flow in the resting forearm during contralateral isometric handgrip were investigated together with the respiratory sinus arrhythmia (measured during standardized breathing frequency and depth), and the heart rate response to a Valsalva manoeuvre in 20 patients with insulin-dependent diabetes and clinical signs of a peripheral neuropathy. The respiratory sinus arrhythmia and the Valsalva ratio were attenuated in the patients compared to age-matched controls, indicating reduced vagal function. Also the responses to handgrip were reduced. The blood flow increase in the resting forearm upon handgrip was correlated with both the respiratory sinus arrhythmia and the Valsalva ratio, supporting neurogenic mediation of the flow response and indicating a reduction in sympathetic as well as vagal function in diabetes autonomic neuropathy.     

Direct vasodilator effects of physiological hyperinsulin-aemia in human skeletal muscle

Systemic hyperinsulinaemia induces vasodilatation in human skeletal muscle. This effect is gradual in onset, and at low insulin levels not maximal until at least 3 h. To investigate whether the vasodilator response to insulin results from a direct vascular effect, we infused insulin directly into the cannulated brachial artery (perfused forearm technique) in a total of 30 experiments in 20 healthy, lean, normotensive volunteers. Local, intra-arterial, infusion of insulin (180 min, 0.3 mU dL^?1 forearm volume min^?1, n = 15, forearm venous insulin concentration approximately 540 pmol L^?1) induced a gradual increase in forearm blood flow (FBF; venous occlusion plethysmography) from 1.86 ± 0.17 to 3.64 ± 0.64 mL dL^?1 min^?1 after 180 min (anova P < 0.001). Percentage increases in FBF after 60, 120 and 180 min averaged 14.4 ± 5.9, 59.4 ± 25.5 and 124.6 ± 51.2% respectively. Forearm glucose uptake increased from 0.24 ± 0.05 to a maximum of 1.98 ± 0.28 μmol dL^?1 min (P < 0.001). Furthermore, insulin infusion increased forearm lactate release and potassium uptake. In 10 out of these 15 individuals, the forearm glucose uptake was further increased in a second, separate, repeat experiment with concomitant intra-arterial infusion of glucose 5% (0.2 mL dL^?1 min^?1), resulting in forearm venous glucose concentrations of approximately 15 mmol L^?1. This combined infusion achieved a similar vasodilator response to the infusion of insulin alone. The individual vascular responses of the two paired experiments showed a strong correlation (r = 0.87, P < 0.01). In five subjects time and vehicle control experiments were performed, showing no changes in FBF or metabolism during the 180 min. We conclude that the slow vasodilator response to insulin (as observed during systemic infusion) can, at least partly, be explained by a direct vascular effect of insulin. Insulin-mediated skeletal muscle glucose uptake precedes this effect, but seems not to be an important determinant of the vasodilator response to insulin.     

Orthostatic reactions during recovery from exhaustive exercise of short duration

We studied the responses of six healthy volunteers to standard 70° head-up tilt tests before exhaustive exercise of short duration (control) and after 5, 25, 50, 80, and 110 min of recovery, all tests lasting for 6 min except when impending syncope (IS) necessitated premature termination of a test. Marked impairment of orthostatic tolerance was apparent during the first half-hour of recovery as manifested by symptoms of IS in five subjects in one or both of the first two postexercise tilt tests. In none of the subjects who developed symptoms of IS did central venous pressure fall to a lower level than it did in the control test. From the central venous and arterial pressure reactions we conclude that when IS developed, declining systematic resistance rather than diminished cardiac filling was the responsible factor. The increased tendency for orthostatic collapse occurred during a period of recovery marked by persistent postexercise acidemia and hyperthermia suggesting interference of these conditions and associated events with the normal ability to vasoconstrict during orthostasis     

Bacterial infections in cirrhosis.

Spontaneous bacterial peritonitis, urinary tract infections, respiratory infections and bacteremia are the most frequent infective complications in cirrhosis. These infections are due to the concomitant presence of different facilitating mechanisms including changes in the intestinal flora and in the intestinal barrier, depression of activity of the reticuloendothelial system, decreased opsonic activity of the ascitic fluid, neutrophil leukocyte dysfunction and iatrogenic factors among others. The fact, that the probability of having a microorganism responsible for the infection quinolone resistant is higher than 30% should be taken into account when treating any infection in a cirrhotic patient receiving selective intestinal decontamination with quinolones, and therefore, quinolones as empiric treatment are not indicated.     

Stimulation of an intracranial trigeminally-innervated structure selectively increases cerebral blood flow

The cranial circulation, both extracerebral and cerebral, is innervated by fibers from the trigeminal nerve. This system is known as the trigeminovascular system. The large venous sinuses and dura mater are pain-sensitive and are innervated primarily by branches of the ophthalmic division of the trigeminal nerve. Studies were conducted in the α-chloralose anaesthetised cat to examine bulk carotid and cerebral blood flow responses to electrical stimulation of the trigeminal ganglion and superior sagittal sinus. Bulk carotid blood flow was measured using an ultrasonic flow probe and meter applied to the common carotid artery while cerebral blood flow was measured using laser Doppler flowmetry. Vascular resistance was calculated using simultaneously collected blood pressure data. Stimulation of the trigeminal ganglion resulted in a frequency-dependent reduction in both bulk carotid and cerebral vascular resistance. The mean maximal reduction was 39±5% at 20/s for the carotid bed and 37±6% at 20/s for the cerebral circulation. Stimulation of the superior sagittal sinus resulted in a frequency-dependent reduction in resistance that involved the cerebral circulation with little effect on bulk carotid resistance. The mean maximum reduction was 37±6% at 20/s for the cerebral circulation and 11±3% at 2/s for bulk carotid resistance. The more focused effects of superior sagittal sinus suggest a highly organised somatotopic arrangement of the trigeminal innervation of the cranial circulation. Such a physiological schema fits the known anatomy as reflected by the differential peptidergic innervation from the trigeminovascular system to cranial vessels and may be important in understanding the pathophysiology of migraine, cluster headache and subarachnoid haemorrhage. ©1997 Elsevier Science B.V. All rights reserved.     

Optimal structure of the arterial network of skeletal muscles

A criterion of optimal structure of the arterial network of a skeletal muscle is suggested, namely minimization of its hydraulic resistance during intensive work. By the use of this criterion the ratio between the mean diameter of the vessels of different orders of branching can be determined. Equations were obtained showing dependence of the hydraulic resistance, volume, and pressure in vessels of different caliber on the order of branching. Rough quantitative estimates of the possible increase in blood flow in an intensively working muscle compared with the same muscle at rest are given.Department of Physics of Living Systems, Moscows Physicotechnical Institute. Laboratory of Biophysics and Pathophysiology of the Circulation, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 9, pp. 259–262, September, 1978.