Final proof Starling’s law wrong and G tube hydrodynamic is the correct replacement: New results and critical analytical criticisms of landmark articles

Substantial evidence demonstrating Starling’s law is wrong currently exists. This article presents the final definitive proof that Starling’s law is wrong, and the correct replacement is the hydrodynamic of the G tube. The presented evidence is based on reported and new results of the G tube hydrodynamic and critical analytical criticism of landmark and contemporary impactful articles. The objectives of this article are to affirm applicability to capillary; crossing the editors’ barrier to convince the hardest of critics that the new theory is correct. The new results presented here further affirm this and the critical analytical criticisms reveal many errors that has misled authors into reporting erroneous results and conclusions affirming Starling’s law and its equations are wrong. The new results show the difference between the hydrostatic pressure and the two components of dynamic pressure: Flow and Side pressures. The side pressure is a negative pressure gradient exerted on the wall of G tube built on a scale to capillary ultrastructure of precapillary sphincter and the wide intercellular cleft pores in its wall. This affirms Starling’s law and its equation are wrong and its correct replacement is the magnetic field like phenomenon of the G tube that explain the fast capillary interstitial fluid transfer necessary for viability of cells at rest and during strenuous exercise.

Precapillary sphincters control cerebral blood flow

Active nerve cells produce and release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling, which is the basis of the BOLD (blood-oxygen-level-dependent) functional neuroimaging signals. We here reveal a unique mechanism for cerebral blood flow control, a precapillary sphincter at the transition between the penetrating arteriole and the first capillary that links blood flow in capillaries to the arteriolar inflow. Large NG2-positive cells, containing smooth muscle actin, encircle the sphincters and rises in nerve cell activity cause astrocyte and neuronal Ca2+ rises that correlate to dilation and shortening of the sphincter concomitant with substantial increases in the RBC flux. Global ischemia and cortical spreading depolarization constrict sphincters and cause vascular trapping of blood cells. These results reveal precapillary sphincters as bottlenecks for brain capillary blood flow.

Capillary filtration coefficient is independent of number of perfused capillaries in cat skeletal muscle

The capillary filtration coefficient (CFC) is assumed to reflect both microvascular hydraulic conductivity and the number of perfused capillaries at a given moment (precapillary sphincter activity). Estimation of hydraulic conductivity in vivo with the CFC method has therefore been performed under conditions of unchanged vascular tone and metabolic influence. There are studies, however, that did not show any change in CFC after changes in vascular tone and metabolic influence, and these studies indicate that CFC may not be influenced by alteration in the number of perfused capillaries. The present study reexamined to what extent CFC in a pressure-controlled preparation depends on the vascular tone and number of perfused capillaries by analyzing how CFC is influenced by 1) vasoconstriction, 2) increase in metabolic influence by decrease in arterial blood pressure, and 3) occlusion of precapillary microvessels by arterial infusion of microspheres. CFC was calculated from the filtration rate induced by a fixed decrease in tissue pressure. Vascular tone was increased in two steps by norepinephrine ( n = 7) or angiotensin II ( n = 6), causing a blood flow reduction from 7.2 ± 0.8 to at most 2.7 ± 0.2 ml · min−1 · 100 g−1( P < 0.05). The decrease in arterial pressure reduced blood flow from 4.8 ± 0.4 to 1.40 ± 0.1 ml · min−1 · 100 g−1( n = 6). Vascular resistance increased to 990 ± 260% of control after the infusion of microspheres ( n= 6). CFC was not significantly altered from control after any of the experimental interventions. We conclude that CFC under these conditions is independent of the vascular tone and number of perfused capillaries and that variation in CFC reflects variation in microvascular hydraulic conductivity.

Mathematical analysis of the relationship between blood flow and uptake of nutrients in the mammary glands of a lactating cow

SummaryA dynamic mathematical model of blood flow regulation in the mammary glands of a lactating cow was constructed from a principle of local vasodilator release in response to changes in intracellular adenylate charge. An equation was derived to predict uptake of the milk precursors acetate, glucose, amino acids and fatty acids, as affected by mammary blood flow rate. Metabolism of the precursors to milk components and CO2 was simulated with a set of empirically derived equations. Relative rates of ATP production and utilization regulated both the number of perfused capillaries and the conductance of arteriolar segments in the mammary glands. The model simulated local control phenomena of functional and reactive hyperaemia, and simulation of autoregulation under changing arterial pressure suggested a predominance of precapillary sphincter regulation. It was predicted that an increase in blood flow without the mammary capacity to utilize blood metabolites efficiently would be detrimental to milk synthesis. Conversely, increased blood flow through changes in mammary activity resulted in predictions of higher milk production. It was proposed that the equation for uptake,be used in analysis of mammary arteriovenous differences.

Regulation of capillary exchange capacity in the dog stomach

The capillary exchange capacity of the isolated, perfused dog stomach was investigated during vasoconstriction (norepinephrine) and vasodilation (isoproterenol) and compared with values obtained when blood flow to the stomach was decreased or increased mechanically. The capillary filtration coefficient (Kf,c) was used as an index of capillary exchange capacity. Under resting conditions, Kf,c in the isolated stomach was 0.20 +/- 0.02 ml . min-1 . mmHg-1 . 100 g-1. Vasoconstriction and mechanical reduction in blood flow caused Kf,c to fall to 68 and 58% of control, while vasodilation and mechanical increase in blood flow caused Kf,c to rise to 176 and 231% of control, respectively. Pentagastrin produced an increase in gastric oxygen consumption and a 50% increase in Kf,c. In all instances, capillary exchange capacity appeared to be correlated with gastric blood flow. The data suggest there is little local control of precapillary sphincter tone in the stomach and that capillary exchange capacity may be governed by local pressure within the microvasculature.

Simultaneous estimation of arteriolar, capillary, and shunt blood flow of the gut mucosa

Microspheres of 15 and 9 microns diameter were injected simultaneously into the left ventricle of the dog, and the entrapment of these microspheres in different layers of the gut wall was measured under resting conditions, vasoconstriction, and subsequent vasodilation. Results show that some of the 9-microns spheres passed into the portal blood through all layers of the gut wall, whereas 15-microns spheres were completely entrapped in the tissue. The pattern of entrapment of 15-microns spheres during vasoconstriction and during subsequent vasodilation suggests that these microspheres measure adequately the arteriolar inflow of the muscularis, submucosa, and mucosa (i.e., villus plus crypt) but, due to series arrangement between the arterioles of the villus and the crypt, cannot measure the arteriolar flow of the villus and crypt separately. The entrapment of 9-microns microspheres in the muscularis, submucosa, crypt, and villus that occurred during vasoconstriction did not change during subsequent vasodilation. This suggests that these microspheres became lodged in the precapillary sphincter or capillary and therefore measured the capillary flow of these layers. Accordingly, the difference between the arteriolar (measured by 15 microns) and the capillary (measured by 9 microns) flow of the muscularis, submucosa, and mucosa may provide an estimate of the noncapillary (shunt) flow of these layers.

Frequency analysis of coronary intercapillary distances: site of capillary control

Frequency distributions for minimum intercapillary distance (ICD) and functional ICD were characterized for rat heart in situ. Minimum ICD denotes spacings between adjacent capillaries whether they contain erythrocytes or not.Functional ICD is defined as spacings between contiguous capillaries perfused with erythrocytes. Minimum ICD was well fitted by both the gamma and the lognormal distributions. Functional ICD was well fitted by the lognormal, but not by the gamma, or by any mixture of the gamma with another discrete distribution. The frequency analysis is interpreted to mean that: 1) A control site distal to the true arteriole exists. This is presumably the precapillary sphincter. 21 Intercapillary anastomoses help keep the diffusion path in myocardium short and comparatively uniform. 3) Complete closure of arterioles does not occur in the unstressed heart. 4) Blood flow and conditions for diffusion can be controlled independently.

Central neural influence on precapillary microvessels and sphincter

The responses to central nervous system (CNS) stimulation of consecutive segments of arterioles down to the precapillary sphincter were measured in the mesoappendix and/or cremaster of nine male rats with indwelling electrodes. Under pentobarbital sodium anesthesia, vasoactive sites were stimulated at threshold for maximal constriction or lumen closure of the precapillary sphincter and/or immediately preceding precapillary arteriole (metarteriole). In all experiments, CNS stimulation induced blood pressure elevation and constriction of three consecutive segments of precapillary vessels and of the sphincter. A threefold increase in rate of vasomotion of precapillary sphincter and metarteriole was the rule, but this was noted infrequently in larger arterioles. In addition to an overall influence of the CNS on microcirculation, the data show a gradient of responses to stimulation, the slope of which is negatively related to the size of the vessels and sphincter, in both tissues studied. A complete lumen closure of the metarteriole and precapillary sphincter (when present) in response to CNS stimulation implies active participation in the regulation of local blood flow. No evidence was foun for central neural regulation of the precapillary sphincter independent of arteriolar control.

An analysis of interstitial fluid pressure in the web of the bat wing

A mathematical theory of interstitial fluid motion and capillary exchange is developed in order to understand and explain measurements of capillary and interstitial fluid pressure in the bat wing, in which a high degree of vasomotor activity occurs. As a result of precapillary sphincter activity, fluid is alternately filtered and reabsorbed from the capillary, and previous studies of related steady problems by the author suggest that the interstitial fluid pressure should oscillate with time. Wiederhielm and Weston did not observe such fluctuations when they measured tissue pressures near the capillaries. This apparent paradox is resolved in the present paper by including unsteady effects. It is shown that pressure oscillations are predicted, but because of the very high vasomotor frequency they die out within a very short distance from the capillary wall. The capillary pressure measurements of Wiederhielm and Weston are also explained in terms of precapillary sphincter activity.