Cardiovascular benefits in moderate increases of blood and plasma viscosity surpass those associated with lowering viscosity: Experimental and clinical evidence.

Decreasing blood viscosity has been proposed since the advent of hemodilution as a means for increasing perfusion in many pathological conditions, and increased plasma viscosity is associated with the presence of pathological conditions. However, experimental studies show that microvascular functions as represented by functional capillary density in conditions of significantly decreased viscosity is impaired, a problem corrected by increasing plasma and blood viscosity. Blood viscosity, primarily dependent on hematocrit (Hct) is a determinant of peripheral vascular resistance, and therefore blood pressure. In the healthy population Hct presents a variability, which is not reflected by the variability of blood pressure. This is due to a regulatory process at the level of the endothelium, whereby the increase of Hct (and therefore blood viscosity) leads to increased shear stress and the production of the vasodilator nitric oxide (NO), a finding supported by experimental studies showing that the acute increase of Hct lowers blood pressure. Studies that in the healthy population show that blood pressure and Hct have a weak positive correlation. However, when the effect of blood viscosity is factored out, blood pressure and Hct are negatively and significantly correlated, indicating that as blood viscosity increases, the circulation dilates. Conversely, lower Hct and blood viscosity conditions lead to a constricted circulation, associated with a condition of decreased NO bioavailability, and therefore a pro-inflammatory condition.

Microvascular benefits of increasing plasma viscosity and maintaining blood viscosity: counterintuitive experimental findings.

The circulation is adapted to specific levels of blood viscosity resulting in a balance that simultaneously sets peripheral vascular resistance, blood pressure and cardiac output, factors in part mediated by the production of nitric oxide by the endothelium. Although it is generally perceived that decreasing blood viscosity is beneficial for cardiovascular function, small increases of blood viscosity in normal healthy experimental subjects significantly improve cardiovascular function. These changes are within the normal variations of viscosity due to the variations of hematocrit in the healthy population. Hemodilution reduces blood viscosity, which is proposed to be physiologically beneficial. However, in extreme hemodilution, increased plasma viscosity via the use of viscogenic plasma expanders sustains microvascular and tissue function at significantly reduced levels of oxygen delivery. Studies in hemorrhagic shock resuscitation using oxygen carrying and non-carrying red blood cells show that restoration of blood viscosity is as important as restoration of oxygen carrying capacity. It is concluded that although hemodilution is indicated for reducing abnormally high blood viscosities, it is beneficial to increase plasma viscosity when hematocrit is reduced. Furthermore small increases in hematocrit may be beneficial due to the related increase in blood viscosity, independently of the increase of oxygen delivery capacity.

Beneficial effects due to increasing blood and plasma viscosity.

Increased plasma and blood viscosity are usually associated with pathological conditions; however there are several situations in which the elevation of both parameters results in increased perfusion and the lowering of peripheral vascular resistance. In extreme hemodilution blood viscosity is too low and insufficient to maintain functional capillary density, a problem that in experimental studies is shown to be corrected by increasing plasma viscosity up to 2.2 cP. This effect is mediated by Nitric oxide (NO) production via restoration of shear stress at the endothelium as shown by microelectrode perivascular measurements of NO concentration. Moderate elevations of blood viscosity by increasing hematocrit (approximately 10% of baseline) result in reductions of blood pressure by 10 mmHg of baseline. This effect is also NO mediated since it is absent after N-nitro-L-arginine methyl ester (L-NAME) treatment and in endothelial NO synthase deficient mice. These results show that the rheological properties of plasma affect vessel diameter in the microcirculation leading to counterintuitive responses to the increase in viscosity.

Starch-hemoglobin induces contraction on isolated rat aortic rings.

BACKGROUND: Blood substitutes are being developed using molecular solutions of modified free hemoglobin; however, anaphylactic reactions, severe renal toxicity, and hypertension have been reported in experimental models and human beings. Hypertension remains as an obstacle to the clinical use of most blood substitutes. Several investigators suggest that this effect is due to the interaction between nitric oxide and hemoglobin into the endothelial cells; hence, prevention of hemoglobin extravasation would avoid vasoconstriction. The forms of hemoglobin likely to prevent extravasation include polymerized and encapsulated Hb. Another alternative and significantly less expensive approach is the hydroxyethyl starch Hb-polymer. The aim of the present study was to compare the effect of hydroxyethyl-starch-hemoglobin with that of stroma-free hemoglobin on the in vitro contractile activity of aortic rings isolated from adult male rats. METHODS: The hemoglobin-based oxygen carrier was made using stroma-free hemoglobin prepared from outdated human red cells and conjugated with 10% hydroxyethyl starch 200-260 MW. The experiments were made in thoracic segments of the aortic rings incubated with hemoglobin, starch-hemoglobin or Ringer Krebs-Bicarbonate solution (RKB) during 30 min. Smooth muscle contraction with phenylephrine and subsequent inhibition of contraction with carbachol were performed before and after incubation with hemoglobin, starch-hemoglobin, or vehicle. RESULTS: Incubation with hemoglobin and starch-hemoglobin significantly increased the contractile response to phenylephrine of aortic rings compared with RKB solution. The maximal response to carbachol was significantly decreased in the aortic rings incubated with either hemoglobin or starch-hemoglobin in comparison with the RKB-incubated tissues. There were no differences between the aortic rings incubated with either hemoglobin, or starch-hemoglobin. CONCLUSIONS: These results show that there are no differences between the effects of stroma-free hemoglobin and starch-hemoglobin on the in vitro contractile activity of aortic rings isolated from adult male rats. Our findings do not support the hypothesis that an increase in the size of the hemoglobin molecule prevents hemoglobin extravasation, and the consequent vasoconstriction due to the scavenging of nitric oxide by stroma free hemoglobin in the cellular space between endothelium and smooth muscle.

[Myocardial bridging. The role of microcirculation, coronary reserve and systolic endothelial injury]. / Puentes miocárdicos. Papel de la microcirculación, reserva coronaria y daño endotelial sistólico.

BACKGROUND: The relationship between myocardial bridging (MB) and ischemic heart disease is still controversial. However, a recent new evidence suggests that this relation is not by chance. PURPOSE: The purpose of our study was to review in a critical manner, the evidence for the relationship between MB and myocardial ischemia and its possible consequences. METHODS: We present 2 cases of our series and review the medical literature from January 1966 to January 1998 published and included in Medline and Current Contents. RESULTS AND CONCLUSIONS: The principal findings after this review were: 1) MB is not a normal variant; 2) The clinical impact of MB depends on its anatomical extension and degree of compressive effect; 3) The MB muscle is not similar to myocytes from other cardiac areas; 4) The environment surrounding coronary artery may be a crucial factor in determining whether the MB influences the induction of heart disorders or not; 5) The overshoot due to compressive effect on coronary artery might determine endothelial injury in the microcirculation post-MB; 6) In some cases, the systolic endothelial injury may contribute to release factors that are able to reduce the coronary reserve, resulting in myocardial ischemia; 7) The possible role of PTCA in this disorder still has to be proven. Surgical treatment should be considered when important myocardial ischemia had been demonstrated, even in those asymptomatic cases.

Control of myocardial reperfusion injury with hypertonic-hyperosmotic solution in isolated rabbit heart.

The effects of postischemic reperfusion were investigated in 14 isolated rabbit hearts in Langendorff preparation. Seven were controls and the others were reperfused with a sodium 7.5% and dextran 60 (60,000 MW) solution diluted with Krebs-Henseleit buffer to a sodium concentration of 150 mEq/l. The incidence of arrhythmias was lower in this group (p = 0.034). Coronary flow was higher than in controls (p = 0.035), the levels of isoenzyme MB of creatine kinase were lower than in controls (p = 0.035), myocardial water content was also lower (p = 0.047), and histological damage was reduced (p = 0.018). It was concluded that early reperfusion with 7.5% sodium chloride, 6% dextran 60 solution has a protective effect in the treatment of cardiac reperfusion injury.

Treatment of hemorrhagic shock with intraosseous or intravenous infusion of hypertonic saline dextran solution.

The efficacy of intravenous or intraosseous infusion of 250 ml of 7.5% NaCl and 6% dextran 60 (H/H) was compared with intravenous Ringer's lactate (RL) for the initial treatment of patients with hemorrhagic shock due to upper gastrointestinal bleeding. 49 patients were randomly assigned to receive either H/H (n = 26) or RL (n = 23). In the first 16 patients with H/H and in all RL patients, solutions were infused by the intravenous route, while the intraosseous route through sternal puncture was chosen for the last 10 H/H subjects. H/H patients were analyzed together since no differences were noticed between the routes of infusion. The H/H group also received 2.3 +/- 0.7 liters of intravenous crystalloid solutions in the first hour and 4.4 +/- 0.1 liters in the 24-hour period, while RL received 3.3 +/- 0.7 and 7.3 +/- 2.4 liters, respectively. Blood pressure (BP) increased during the first 15 min in the H/H group (from 61 +/- 17/30 +/- 12 to 85 +/- 30/48 +/- 14 mm Hg) and thereafter, while remaining unchanged in the RL group (from 75 +/- 18/40 +/- 12 to 75 +/- 17/40 +/- 14 mm Hg; p less than 0.05). The differences between groups were significant throughout 24 h. Urine output and improvement of the Glasgow Coma Score were also higher in H/H patients than in the control group (p less than 0.05). There were 5 deaths in RL group and 1 in the H/H group. Sternal of peripheral vein infusion of 250 ml of 7.5% NaCl/6% dextran 60 is an effective initial treatment of hemorrhagic shock.

Influence of nopal intake upon fasting glycemia in type II diabetics and healthy subjects.

To assess if the acute hypoglycemic effect of nopal which occurs in diabetic patients also appears in healthy individuals, 500 g of nopal stems (O. streptacantha Lem.) were given orally to 14 healthy volunteers and to 14 patients with NIDDM. Serum glucose and insulin levels were measured at 0, 60, 120 and 180 minutes after nopal ingestion. A control test was performed with the intake of 400 ml of water. The intake of nopal by the NIDDM group was followed by a significant reduction of serum glucose and insulin concentration reaching 40.8 + 4.6 mg/dl (n = 14) (mean+SEM) and 7.8 + 1.5 uU/ml (n = 7) less than basal value, respectively, at 180 minutes. (P less than 0.001 vs control test). No significant changes were noticed in the healthy group as compared with the control test (P greater than 0.05). Acute hypoglycemic effect of nopal was observed in patients with NIDDM but not in healthy subjects, thus the mechanisms of this effect differs from current hypoglycemic agents.

[Activity of Opuntia streptacantha in healthy individuals with induced hyperglycemia]. / Acción de Opuntia streptacantha en individuos sanos con hiperglucemia inducida.

Hypoglycemia effect Opuntia streptacantha which occur in diabetic has not been found in healthy subjects. To find out if this effect appears also in healthy individuals if they are hyperglycemic, two tests were performed to 7 healthy volunteers. In both tests 500 ml of 20% dextrose were infused in two hours, 500 g of O. streptacantha were given orally before one test, and 400 ml of water as control were given before the other one. Serum glucose was measured every 30 minutes during three hours. Glucose rising was significantly (P less than 0.025) lower with Opuntia than in control test at 90 and 120 minutes (143 +/- 58 vs 193 +/- 9 and 135 +/- 25 vs 163 +/- 13 mg/dl respectively). Area under curve of glucose was also smaller in Opuntia than in control test (P less than 0.05). Hypoglycemic effect of O. streptacantha also occur in healthy subjects in hyperglycemia is present.

[Effect of different doses of Plantago psyllium mucilage on the glucose tolerance test]. / Efecto de diferentes dosis de mucílago de Plantago psyllium en la prueba de tolerancia a la glucosa.

To assess the effect of different doses of Plantago psyllium mucilage on glucose tolerance test, four oral glucose tolerance tests were performed to eight healthy volunteers. Glucose load (75 g) was mixed with 0 (control test), 10.20 and 30 g of mucilage. Serum glucose levels were measured at 0, 30, 60, 120 and 180 minutes. Maximum peak of glucose at 30 minutes, and the area under the curve of glucose were significantly lower in the test with 20 and 30 g of mucilage than the tests with 0 and 10g. There was a significant relationship (r = 0.44 p less than 0.025) between the dose of P. psyllium mucilage and its attenuating effect of hyperglycemia.

[Hypoglycemic action of different doses of nopal (Opuntia streptacantha Lemaire) in patients with type II diabetes mellitus]. / Acción hipoglucemiante de diferentes dosis de nopal (Opuntia streptacantha Lemaire) en pacientes con diabetes mellitus tipo II.

To assess the relationship between the doses of O. streptacantha Lem. and its acute hypoglycemic action in diabetics, eight patients with type II diabetes mellitus were studied. Four test were performed to each patient with the intake of: (a) 400 ml of water, (b) 100 g (c) 300 g and (d) 500 g of broiled stems of O. streptacantha Lem. Serum glucose was measured at 0, 60, 120 and 180 minutes. Maximal decrease of serum glucose was noticed at 180 minutes, with a mean of 2.3, 10, 30.1 and 46.7 mg/dl less than basal value with 0, 100, 300 and 500 g respectively (P = NS, less than 0.05, less than 0.001 and less than 0.001 respectively). A significant direct correlation (r = 0.690, P less than 0.001) was noticed between the doses and the hypoglycemic effect.

Estudios hormonales en la accion del nopal sobre la prueba de tolerancia a la glucosa. Informe preliminar. / Hormonal studies in the nopal action on the glucose tolerance test. Preliminary report

Para investigar si la accion "hipoglucemiante" del nopal se explica por menores concentraciones sanguineas de las hormonas hiperglucemiantes, se estudiaron cuatro voluntarios sanos con dos pruebas de tolerancia a la glucosa por via bucal, una de ellas con previa ingestion de 100 g de tallos de nopal asados. Se midieron glucagon cortisol y hormona de crecimiento, asi como insulina y glicosa en sangre, a los 0, 60, 120 y 180 minutos. La glucosa y la insulina resultaron menores en la prueba con nopal, mientras que los niveles de glucagon, cortisol y hormona de crecimiento no mostraron diferencias significativas entre las dos pruebas. Glucagon, cortisol y hormona de crecimiento no parecen intervenir en la accion "hipoglucemiante" del nopal

HLA-DR antigens in Mexican patients with Guillain-Barré syndrome.

The distribution of HLA-DR antigens was investigated in 38 Mexican Mestizo patients with Guillain-Barré syndrome (GBS) and in 100 healthy controls belonging to the same population. IgG, IgM, IgA, CH50, C3, C4 and the number of T and B lymphocytes were also evaluated in the patients. Only DR3 was significantly increased in the patients (Yates' chi 2 = 9.943, Pc = 0.014) and the relative risk for developing the disease was 3.49. These findings support the hypothesis that DR3 or a closely linked Ir gene may play some role in the susceptibility to GBS.